1qcm - Revision history

OCA at 09:19, 6 December 2023

OCA — Wed, 06 Dec 2023 09:19:09 GMT

←Older revision		Revision as of 09:19, 6 December 2023
Line 1:		Line 1:

	==AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES==		==AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES==
-	<StructureSection load='1qcm' size='340' side='right'caption='[[1qcm~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>	+	<StructureSection load='1qcm' size='340' side='right'caption='[[1qcm]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QCM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QCM FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [https://pdbe.org/1qcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [https://www.ebi.ac.uk/pdbsum/1qcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qcm ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [https://pdbe.org/1qcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [https://www.ebi.ac.uk/pdbsum/1qcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qcm ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[https://omim.org/entry/104300 104300]]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:8476439</ref> <ref>PMID:15201367</ref> <ref>PMID:1671712</ref> <ref>PMID:1908231</ref> <ref>PMID:1678058</ref> <ref>PMID:1944558</ref> <ref>PMID:1925564</ref> <ref>PMID:1415269</ref> <ref>PMID:1303239</ref> <ref>PMID:1302033</ref> <ref>PMID:1303275</ref> <ref>PMID:8267572</ref> <ref>PMID:8290042</ref> <ref>PMID:8577393</ref> <ref>PMID:9328472</ref> <ref>PMID:9754958</ref> <ref>PMID:10097173</ref> <ref>PMID:10631141</ref> <ref>PMID:10665499</ref> <ref>PMID:10867787</ref> <ref>PMID:11063718</ref> <ref>PMID:11311152</ref> <ref>PMID:11528419</ref> <ref>PMID:12034808</ref> <ref>PMID:15365148</ref> <ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:[https://omim.org/entry/605714 605714]]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:10821838</ref> <ref>PMID:2111584</ref> <ref>PMID:11409420</ref> <ref>PMID:12654973</ref> <ref>PMID:16178030</ref>	+	[https://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[https://omim.org/entry/104300 104300]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:8476439</ref> <ref>PMID:15201367</ref> <ref>PMID:1671712</ref> <ref>PMID:1908231</ref> <ref>PMID:1678058</ref> <ref>PMID:1944558</ref> <ref>PMID:1925564</ref> <ref>PMID:1415269</ref> <ref>PMID:1303239</ref> <ref>PMID:1302033</ref> <ref>PMID:1303275</ref> <ref>PMID:8267572</ref> <ref>PMID:8290042</ref> <ref>PMID:8577393</ref> <ref>PMID:9328472</ref> <ref>PMID:9754958</ref> <ref>PMID:10097173</ref> <ref>PMID:10631141</ref> <ref>PMID:10665499</ref> <ref>PMID:10867787</ref> <ref>PMID:11063718</ref> <ref>PMID:11311152</ref> <ref>PMID:11528419</ref> <ref>PMID:12034808</ref> <ref>PMID:15365148</ref> <ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:[https://omim.org/entry/605714 605714]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:10821838</ref> <ref>PMID:2111584</ref> <ref>PMID:11409420</ref> <ref>PMID:12654973</ref> <ref>PMID:16178030</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref>	+	[https://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 29:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kobayashi, K]]	+	[[Category: Kobayashi K]]
-	[[Category: Kohno, T]]	+	[[Category: Kohno T]]
-	[[Category: Maeda, T]]	+	[[Category: Maeda T]]
-	[[Category: Sato, K]]	+	[[Category: Sato K]]
-	[[Category: Takashima, A]]	+	[[Category: Takashima A]]
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Alzheimer's disease]]~~	+
-	~~[[Category: Amyloid]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Down's syndrome]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Neurone]]~~	+
-	~~[[Category: Serine protease inhibitor]]~~	+
-	~~[[Category: Transmembrane~~]]	+

OCA at 09:53, 15 September 2021

OCA — Wed, 15 Sep 2021 09:53:40 GMT

←Older revision		Revision as of 09:53, 15 September 2021
Line 3:		Line 3:
	<StructureSection load='1qcm' size='340' side='right'caption='[[1qcm]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='1qcm' size='340' side='right'caption='[[1qcm]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1QCM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QCM FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [~~http~~://pdbe.org/1qcm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1qcm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1qcm ProSAT]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [https://pdbe.org/1qcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [https://www.ebi.ac.uk/pdbsum/1qcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qcm ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[~~http~~://omim.org/entry/104300 104300]]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:8476439</ref> <ref>PMID:15201367</ref> <ref>PMID:1671712</ref> <ref>PMID:1908231</ref> <ref>PMID:1678058</ref> <ref>PMID:1944558</ref> <ref>PMID:1925564</ref> <ref>PMID:1415269</ref> <ref>PMID:1303239</ref> <ref>PMID:1302033</ref> <ref>PMID:1303275</ref> <ref>PMID:8267572</ref> <ref>PMID:8290042</ref> <ref>PMID:8577393</ref> <ref>PMID:9328472</ref> <ref>PMID:9754958</ref> <ref>PMID:10097173</ref> <ref>PMID:10631141</ref> <ref>PMID:10665499</ref> <ref>PMID:10867787</ref> <ref>PMID:11063718</ref> <ref>PMID:11311152</ref> <ref>PMID:11528419</ref> <ref>PMID:12034808</ref> <ref>PMID:15365148</ref> <ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:[~~http~~://omim.org/entry/605714 605714]]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:10821838</ref> <ref>PMID:2111584</ref> <ref>PMID:11409420</ref> <ref>PMID:12654973</ref> <ref>PMID:16178030</ref>	+	[[https://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[https://omim.org/entry/104300 104300]]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:8476439</ref> <ref>PMID:15201367</ref> <ref>PMID:1671712</ref> <ref>PMID:1908231</ref> <ref>PMID:1678058</ref> <ref>PMID:1944558</ref> <ref>PMID:1925564</ref> <ref>PMID:1415269</ref> <ref>PMID:1303239</ref> <ref>PMID:1302033</ref> <ref>PMID:1303275</ref> <ref>PMID:8267572</ref> <ref>PMID:8290042</ref> <ref>PMID:8577393</ref> <ref>PMID:9328472</ref> <ref>PMID:9754958</ref> <ref>PMID:10097173</ref> <ref>PMID:10631141</ref> <ref>PMID:10665499</ref> <ref>PMID:10867787</ref> <ref>PMID:11063718</ref> <ref>PMID:11311152</ref> <ref>PMID:11528419</ref> <ref>PMID:12034808</ref> <ref>PMID:15365148</ref> <ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:[https://omim.org/entry/605714 605714]]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:10821838</ref> <ref>PMID:2111584</ref> <ref>PMID:11409420</ref> <ref>PMID:12654973</ref> <ref>PMID:16178030</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref>	+	[[https://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:08, 27 November 2019

OCA — Wed, 27 Nov 2019 10:08:03 GMT

←Older revision		Revision as of 10:08, 27 November 2019
Line 1:		Line 1:

	==AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES==		==AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES==
-	<StructureSection load='1qcm' size='340' side='right' caption='[[1qcm]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>	+	<StructureSection load='1qcm' size='340' side='right'caption='[[1qcm]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QCM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QCM FirstGlance]. <br>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 1qcm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1qcm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Amyloid precursor protein 3D structures\|Amyloid precursor protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Kobayashi, K]]		[[Category: Kobayashi, K]]
	[[Category: Kohno, T]]		[[Category: Kohno, T]]

OCA at 08:08, 24 February 2018

OCA — Sat, 24 Feb 2018 08:08:57 GMT

←Older revision		Revision as of 08:08, 24 February 2018
Line 1:		Line 1:
		+
	==AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES==		==AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES==
	<StructureSection load='1qcm' size='340' side='right' caption='[[1qcm]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='1qcm' size='340' side='right' caption='[[1qcm]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QCM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QCM FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [http://pdbe.org/1qcm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [http://www.ebi.ac.uk/pdbsum/1qcm PDBsum]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [http://pdbe.org/1qcm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [http://www.ebi.ac.uk/pdbsum/1qcm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1qcm ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 1qcm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1qcm" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Amyloid precursor protein\|Amyloid precursor protein]]
	== References ==		== References ==
	<references/>		<references/>
Line 31:		Line 29:
	[[Category: Sato, K]]		[[Category: Sato, K]]
	[[Category: Takashima, A]]		[[Category: Takashima, A]]
		+	[[Category: Alternative splicing]]
	[[Category: Alzheimer's disease]]		[[Category: Alzheimer's disease]]
	[[Category: Amyloid]]		[[Category: Amyloid]]

OCA at 04:52, 10 September 2015

OCA — Thu, 10 Sep 2015 04:52:45 GMT

←Older revision		Revision as of 04:52, 10 September 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QCM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QCM FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [http://www.ebi.ac.uk/pdbsum/1qcm PDBsum]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [http://pdbe.org/1qcm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [http://www.ebi.ac.uk/pdbsum/1qcm PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 17:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1qcm" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 12:09, 18 December 2014

OCA — Thu, 18 Dec 2014 12:09:29 GMT

←Older revision		Revision as of 12:09, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1qcm\| PDB=1qcm \| SCENE= }}~~	+	==AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES==
-	===AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES===	+	<StructureSection load='1qcm' size='340' side='right' caption='[[1qcm]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_8973180}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1QCM FirstGlance]. <br>
		+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1qcm RCSB], [http://www.ebi.ac.uk/pdbsum/1qcm PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[http://omim.org/entry/104300 104300]]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:8476439</ref> <ref>PMID:15201367</ref> <ref>PMID:1671712</ref> <ref>PMID:1908231</ref> <ref>PMID:1678058</ref> <ref>PMID:1944558</ref> <ref>PMID:1925564</ref> <ref>PMID:1415269</ref> <ref>PMID:1303239</ref> <ref>PMID:1302033</ref> <ref>PMID:1303275</ref> <ref>PMID:8267572</ref> <ref>PMID:8290042</ref> <ref>PMID:8577393</ref> <ref>PMID:9328472</ref> <ref>PMID:9754958</ref> <ref>PMID:10097173</ref> <ref>PMID:10631141</ref> <ref>PMID:10665499</ref> <ref>PMID:10867787</ref> <ref>PMID:11063718</ref> <ref>PMID:11311152</ref> <ref>PMID:11528419</ref> <ref>PMID:12034808</ref> <ref>PMID:15365148</ref> <ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:[http://omim.org/entry/605714 605714]]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:10821838</ref> <ref>PMID:2111584</ref> <ref>PMID:11409420</ref> <ref>PMID:12654973</ref> <ref>PMID:16178030</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref> <ref>PMID:11544248</ref> <ref>PMID:11943163</ref> <ref>PMID:19225519</ref> <ref>PMID:19901339</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The three-dimensional structure of amyloid beta peptide (25-35), which has neurotoxic activity, in lithium dodecyl sulfate micelles was determined by two-dimensional 1H NMR spectroscopy with simulated annealing calculations. A total of 20 converged amyloid beta peptide structures were obtained on the basis of 110 experimental constraints, including 106 distance constraints reduced from the nuclear Overhauser effect (NOE) connectivities and four torsion angle (phi) constraints. The atomic root mean square difference about averaged coordinates is 1.04 +/- 0.25 A for the backbone atoms (N, C alpha, C) and 1.39 +/- 0.27 A for all heavy atoms of the entire peptide. The molecular structure of amyloid beta peptide in membrane-mimicking environment is composed of a short alpha helix in the C terminal position. The three residues from the N-terminus are disordered, but the remaining eight C-terminal residues are well-ordered, which is supported by the RMSD values of the C-terminal region, Lys28-Leu34. In this region, the RMS differences from averaged coordinates are 0.26 +/- 0.11 A for the backbone atoms (N, C alpha, C) and 0.77 +/- 0.21 A for all heavy atoms, which is very low compared with those for the entire peptide. The four amino acid residues from the N-terminus are hydrophilic and the other seven amino acid residues in C-terminus are hydrophobic. So, our results show that the C-terminal region of amyloid beta peptide (25-35) is buried in the membrane and assumes alpha-helical structure, whereas the N-terminal region is exposed to the solvent with a flexible structure. This structure is very similar to membrane-mediated structure of substance P previously reported. The three-dimensional structure of a non-neurotoxic mutant of amyloid beta peptide (25-35), where Asn27 is replaced by Ala, in lithium dodecyl sulfate micelles was also determined. The structure is similar to that of the wild type amyloid beta peptide (25-35) in the C-terminal region, but the N-terminal flexible region is different. The structural comparison of amyloid beta peptide (25-35), its non-neurotoxic mutant and substance P gives a structural basis to understand the mechanism of neurotoxicity caused by amyloid beta peptide.

-	~~==Disease==~~	+	Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment.,Kohno T, Kobayashi K, Maeda T, Sato K, Takashima A Biochemistry. 1996 Dec 17;35(50):16094-104. PMID:8973180<ref>PMID:8973180</ref>
-	~~[[http://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[http://omim.org/entry/104300 104300]]. AD1 is a familial early~~-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of ~~these plaques is~~ the ~~neurotoxic~~ amyloid-beta~~-APP 40-42~~ peptide (~~s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C~~-~~terminal fragments (CTFs~~) ~~and the caspase-cleaved products such as C31 derived from APP, are also implicated~~ in neuronal death.<ref>PMID:8476439</ref><ref>PMID:15201367</ref><ref>PMID:1671712</ref><ref>PMID:1908231</ref><ref>PMID:1678058</ref><ref>PMID:1944558</ref><ref>PMID:1925564</ref><ref>PMID:1415269</ref><ref>PMID:1303239</ref><ref>PMID:1302033</ref><ref>PMID:1303275</ref><ref>PMID:8267572</ref><ref>PMID:8290042</ref><ref>PMID:8577393</ref><ref>PMID:9328472</ref><ref>PMID:9754958</ref><ref>PMID:10097173</ref><ref>PMID:10631141</ref><ref>PMID:10665499</ref><ref>PMID:10867787</ref><ref>PMID:11063718</ref><ref>PMID:11311152</ref><ref>PMID:11528419</ref><ref>PMID:12034808</ref><ref>PMID:15365148</ref><ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-~~related (CAA-APP) [MIM:[http://omim.org/entry/605714 605714]]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels~~. ~~The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages~~, ~~recurrent strokes~~, ~~cerebral ischemia~~, ~~cerebral infarction~~, ~~and progressive mental deterioration~~. ~~Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre~~-~~amyloid lesions or diffuse plaque-like structures~~. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:~~10821838</ref><ref>PMID:2111584</ref><ref>PMID:11409420</ref><ref>PMID:12654973</ref>~~<ref>PMID:~~16178030~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth~~, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the ~~extracellular matrix such as heparin and collagen I and IV~~. ~~The splice isoforms that contain the BPTI domain possess protease inhibitor activity~~. ~~Induces a AGER-dependent pathway that involves activation~~ of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<~~ref~~>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</~~ref~~>	+	</div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~1qcm~~]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA].	+	*[[Amyloid precursor protein\|Amyloid precursor protein]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:008973180</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Kobayashi, K.]]	+	[[Category: Kobayashi, K]]
-	[[Category: Kohno, T.]]	+	[[Category: Kohno, T]]
-	[[Category: Maeda, T.]]	+	[[Category: Maeda, T]]
-	[[Category: Sato, K.]]	+	[[Category: Sato, K]]
-	[[Category: Takashima, A.]]	+	[[Category: Takashima, A]]
	[[Category: Alzheimer's disease]]		[[Category: Alzheimer's disease]]
	[[Category: Amyloid]]		[[Category: Amyloid]]

OCA at 00:17, 25 March 2013

OCA — Mon, 25 Mar 2013 00:17:18 GMT

←Older revision		Revision as of 00:17, 25 March 2013
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-	[[Image:1qcm.png\|left\|200px]]
-
	{{STRUCTURE_1qcm\| PDB=1qcm \| SCENE= }}		{{STRUCTURE_1qcm\| PDB=1qcm \| SCENE= }}
-
	===AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES===		===AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES===
		+	{{ABSTRACT_PUBMED_8973180}}

-	~~{{ABSTRACT_PUBMED_8973180}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:[http://omim.org/entry/104300 104300]]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:8476439</ref><ref>PMID:15201367</ref><ref>PMID:1671712</ref><ref>PMID:1908231</ref><ref>PMID:1678058</ref><ref>PMID:1944558</ref><ref>PMID:1925564</ref><ref>PMID:1415269</ref><ref>PMID:1303239</ref><ref>PMID:1302033</ref><ref>PMID:1303275</ref><ref>PMID:8267572</ref><ref>PMID:8290042</ref><ref>PMID:8577393</ref><ref>PMID:9328472</ref><ref>PMID:9754958</ref><ref>PMID:10097173</ref><ref>PMID:10631141</ref><ref>PMID:10665499</ref><ref>PMID:10867787</ref><ref>PMID:11063718</ref><ref>PMID:11311152</ref><ref>PMID:11528419</ref><ref>PMID:12034808</ref><ref>PMID:15365148</ref><ref>PMID:15668448</ref> Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:[http://omim.org/entry/605714 605714]]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.<ref>PMID:10821838</ref><ref>PMID:2111584</ref><ref>PMID:11409420</ref><ref>PMID:12654973</ref><ref>PMID:16178030</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/A4_HUMAN A4_HUMAN]] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity).<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref> N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).<ref>PMID:9168929</ref><ref>PMID:11544248</ref><ref>PMID:11943163</ref><ref>PMID:19225519</ref><ref>PMID:19901339</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:008973180</ref><references group="xtra"/>	+	<ref group="xtra">PMID:008973180</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kobayashi, K.]]		[[Category: Kobayashi, K.]]

OCA: Protected "1qcm" [edit=sysop:move=sysop]

OCA — Tue, 14 Aug 2012 18:12:48 GMT

Protected "1qcm" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:12, 14 August 2012

OCA at 18:12, 14 August 2012

OCA — Tue, 14 Aug 2012 18:12:47 GMT

←Older revision		Revision as of 18:12, 14 August 2012
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-	{{Seed}}
	[[Image:1qcm.png\|left\|200px]]		[[Image:1qcm.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1qcm", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_1qcm\| PDB=1qcm \| SCENE= }}		{{STRUCTURE_1qcm\| PDB=1qcm \| SCENE= }}

	===AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES===		===AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_8973180}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 8973180 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_8973180}}		{{ABSTRACT_PUBMED_8973180}}

	==About this Structure==		==About this Structure==
-	~~1QCM is a~~ [[~~Single protein~~]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA].	+	[[1qcm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA].

	==Reference==		==Reference==
-	~~Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment., Kohno T, Kobayashi K, Maeda T, Sato K, Takashima A, Biochemistry. 1996 Dec 17;35(50):16094-104.~~ PMID:~~[http://www.ncbi.nlm.nih.gov~~/~~pubmed~~/~~8973180 8973180]~~	+	<ref group="xtra">PMID:008973180</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Single protein]]
	[[Category: Kobayashi, K.]]		[[Category: Kobayashi, K.]]
	[[Category: Kohno, T.]]		[[Category: Kohno, T.]]
Line 31:		Line 18:
	[[Category: Sato, K.]]		[[Category: Sato, K.]]
	[[Category: Takashima, A.]]		[[Category: Takashima, A.]]
-	[[Category: Alternative splicing]]
	[[Category: Alzheimer's disease]]		[[Category: Alzheimer's disease]]
	[[Category: Amyloid]]		[[Category: Amyloid]]
Line 39:		Line 25:
	[[Category: Neurone]]		[[Category: Neurone]]
	[[Category: Serine protease inhibitor]]		[[Category: Serine protease inhibitor]]
-	[[Category: Signal]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:36:07 2008''

OCA at 16:36, 27 July 2008

OCA — Sun, 27 Jul 2008 16:36:10 GMT

←Older revision		Revision as of 16:36, 27 July 2008
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-	[[Image:1qcm.~~jpg~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:1qcm.png\|left\|200px]]

	<!--		<!--
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	{{STRUCTURE_1qcm\| PDB=1qcm \| SCENE= }}		{{STRUCTURE_1qcm\| PDB=1qcm \| SCENE= }}

-	~~'''~~AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES~~'''~~	+	===AMYLOID BETA PEPTIDE (25-35), NMR, 20 STRUCTURES===


-	~~==Overview==~~	+	<!--
-	The ~~three-dimensional structure of amyloid beta peptide (25-35)~~, ~~which has neurotoxic activity~~, in lithium dodecyl sulfate micelles was determined by two-dimensional 1H NMR spectroscopy with simulated annealing calculations. A total of 20 converged amyloid beta peptide structures were obtained on the ~~basis of 110 experimental constraints, including 106 distance constraints reduced from~~ the ~~nuclear Overhauser effect~~ (~~NOE) connectivities and four torsion angle (phi) constraints. The atomic root mean square difference about averaged coordinates is 1.04 +~~/~~- 0.25 A for the backbone atoms (N, C alpha, C) and 1.39 +~~/~~- 0~~.~~27 A for all heavy atoms of the entire peptide~~. The molecular structure of amyloid beta peptide in membrane-mimicking environment is composed of a short alpha helix in the C terminal position. The three residues from the N-terminus are disordered, but the remaining eight C-terminal residues are well-ordered, which is supported by the RMSD values of the C-terminal region, Lys28-Leu34. In this region, the RMS differences from averaged coordinates are 0.26 +/- 0.11 A for the backbone atoms (N, C alpha, C) and 0.77 +/- 0.21 A for all heavy atoms, which is very low compared with those for the entire peptide. The four amino acid residues from the N-terminus are hydrophilic and the other seven amino acid residues in C-terminus are hydrophobic. So, our results show that the C-terminal region of amyloid beta peptide (25-35) is buried in the membrane and assumes alpha-helical structure, whereas the N-terminal region is exposed to the solvent with a flexible structure. This structure is very similar to membrane-mediated structure of substance P previously reported. The three-dimensional structure of a non-neurotoxic mutant of amyloid beta peptide (25-35), where ~~Asn27~~ is ~~replaced by Ala, in lithium dodecyl sulfate micelles was also determined. The structure is similar to that of~~ the ~~wild type amyloid beta peptide (25-35) in the C-terminal region, but the N-terminal flexible region is different~~. ~~The structural comparison of amyloid beta peptide (25~~-~~35), its non~~-~~neurotoxic mutant and substance P gives a structural basis to understand the mechanism of neurotoxicity caused by amyloid beta peptide.~~	+	The line below this paragraph, {{ABSTRACT_PUBMED_8973180}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 8973180 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_8973180}}

	==About this Structure==		==About this Structure==
-	1QCM is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full ~~crystallographic~~ information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA].	+	1QCM is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCM OCA].

	==Reference==		==Reference==
Line 37:		Line 41:
	[[Category: Signal]]		[[Category: Signal]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May 3 06~~:07:56 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:36:07 2008''