3sv1 - Revision history

OCA at 17:27, 1 November 2023

OCA — Wed, 01 Nov 2023 17:27:04 GMT

←Older revision		Revision as of 17:27, 1 November 2023
Line 3:		Line 3:
	<StructureSection load='3sv1' size='340' side='right'caption='[[3sv1]], [[Resolution\|resolution]] 3.30Å' scene=''>		<StructureSection load='3sv1' size='340' side='right'caption='[[3sv1]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sv1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SV1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sv1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SV1 FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~Mint2 (~~[~~https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=10116 Buffalo rat])~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.3Å</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=3sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sv1 OCA], [https://pdbe.org/3sv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sv1 RCSB], [https://www.ebi.ac.uk/pdbsum/3sv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sv1 ProSAT]</span></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=3sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sv1 OCA], [https://pdbe.org/3sv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sv1 RCSB], [https://www.ebi.ac.uk/pdbsum/3sv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sv1 ProSAT]</span></td></tr>
	</table>		</table>
-	== 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>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/APBA2_RAT APBA2_RAT]] Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP. [[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/APBA2_RAT APBA2_RAT] Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Buffalo rat~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Long, J]]	+	[[Category: Rattus norvegicus]]
-	[[Category: Shen, Y]]	+	[[Category: Long J]]
-	[[Category: Xie, X]]	+	[[Category: Shen Y]]
-	[[Category: Yan, X]]	+	[[Category: Xie X]]
-	~~[[Category: App binding]]~~	+	[[Category: Yan X]]
-	~~[[Category: Protein binding~~]]	+

OCA at 08:11, 29 June 2022

OCA — Wed, 29 Jun 2022 08:11:44 GMT

←Older revision		Revision as of 08:11, 29 June 2022
Line 1:		Line 1:

	==Crystal structure of APP peptide bound rat Mint2 PARM==		==Crystal structure of APP peptide bound rat Mint2 PARM==
-	<StructureSection load='3sv1' size='340' side='right' caption='[[3sv1]], [[Resolution\|resolution]] 3.30Å' scene=''>	+	<StructureSection load='3sv1' size='340' side='right'caption='[[3sv1]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sv1]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3SV1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sv1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SV1 FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mint2 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mint2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sv1 OCA], [~~http~~://pdbe.org/3sv1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3sv1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3sv1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3sv1 ProSAT]</span></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=3sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sv1 OCA], [https://pdbe.org/3sv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sv1 RCSB], [https://www.ebi.ac.uk/pdbsum/3sv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sv1 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/APBA2_RAT APBA2_RAT]] Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP. [[~~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/APBA2_RAT APBA2_RAT]] Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP. [[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 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Buffalo rat]]		[[Category: Buffalo rat]]
		+	[[Category: Large Structures]]
	[[Category: Long, J]]		[[Category: Long, J]]
	[[Category: Shen, Y]]		[[Category: Shen, Y]]

OCA at 14:30, 4 August 2016

OCA — Thu, 04 Aug 2016 14:30:12 GMT

←Older revision		Revision as of 14:30, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of APP peptide bound rat Mint2 PARM==		==Crystal structure of APP peptide bound rat Mint2 PARM==
	<StructureSection load='3sv1' size='340' side='right' caption='[[3sv1]], [[Resolution\|resolution]] 3.30Å' scene=''>		<StructureSection load='3sv1' size='340' side='right' caption='[[3sv1]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3sv1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SV1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3sv1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SV1 FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mint2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 ~~Rattus norvegicus~~])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mint2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sv1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sv1 RCSB], [http://www.ebi.ac.uk/pdbsum/3sv1 PDBsum]</span></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=3sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sv1 OCA], [http://pdbe.org/3sv1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sv1 RCSB], [http://www.ebi.ac.uk/pdbsum/3sv1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sv1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 18:		Line 19:
	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 3sv1" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Rattus norvegicus~~]]	+	[[Category: Buffalo rat]]
	[[Category: Long, J]]		[[Category: Long, J]]
	[[Category: Shen, Y]]		[[Category: Shen, Y]]

OCA at 06:27, 21 December 2014

OCA — Sun, 21 Dec 2014 06:27:40 GMT

←Older revision		Revision as of 06:27, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3sv1\| PDB=3sv1 \| SCENE= }}~~	+	==Crystal structure of APP peptide bound rat Mint2 PARM==
-	===Crystal structure of APP peptide bound rat Mint2 PARM===	+	<StructureSection load='3sv1' size='340' side='right' caption='[[3sv1]], [[Resolution\|resolution]] 3.30Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22730553}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3sv1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SV1 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Mint2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=3sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sv1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sv1 RCSB], [http://www.ebi.ac.uk/pdbsum/3sv1 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>		[[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 ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/APBA2_RAT APBA2_RAT]] Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP. [[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>		[[http://www.uniprot.org/uniprot/APBA2_RAT APBA2_RAT]] Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP. [[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 ==
		+	Amyloid-beta protein precursor (APP) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Knock-out and transgenic mouse studies of the adaptor protein Mint2 have revealed that it is a major player in regulating APP metabolism physiologically through the binding of its PTB domain to the intracellular domain of APP. However, the molecular mechanism of APP dynamically binding to Mint2 remains elusive. Here, we report the structures of APP peptide-free and APP peptide-bound C-terminal Mint2 mutants at resolutions of 2.7 and 3.3 A, respectively. Our structures reveal that APP peptide-free Mint2 exists in a closed state in which the ARM domain blocks the peptide binding groove of the PTB domain. In sharp contrast, APP peptide-bound Mint2 exists in an open state in which the ARM domain drastically swings away from the bound peptide. Mutants that control the open-closed motion of Mint2 dynamically regulated APP metabolism both in vitro and in vivo. Our results uncover a novel open-closed mechanism of the PTB domain dynamically binding to its peptide substrate. Moreover, such a conformational switch may represent a general regulation mode of APP family members by Mint proteins, providing useful information for the treatment of AD.

-	~~==About this Structure==~~	+	Open-closed motion of Mint2 regulates APP metabolism.,Xie X, Yan X, Wang Z, Zhou H, Diao W, Zhou W, Long J, Shen Y J Mol Cell Biol. 2012 Jun 21. PMID:22730553<ref>PMID:22730553</ref>
-	~~[[3sv1]] is a 6 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Rattus_norvegicus Rattus norvegicus]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:022730553</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
-	[[Category: Long, J.]]	+	[[Category: Long, J]]
-	[[Category: Shen, Y.]]	+	[[Category: Shen, Y]]
-	[[Category: Xie, X.]]	+	[[Category: Xie, X]]
-	[[Category: Yan, X.]]	+	[[Category: Yan, X]]
	[[Category: App binding]]		[[Category: App binding]]
	[[Category: Protein binding]]		[[Category: Protein binding]]

OCA at 07:40, 20 June 2013

OCA — Thu, 20 Jun 2013 07:40:02 GMT

←Older revision		Revision as of 07:40, 20 June 2013
Line 4:		Line 4:

	==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>	+	[[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==		==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>	+	[[http://www.uniprot.org/uniprot/APBA2_RAT APBA2_RAT]] Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP. [[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==

OCA at 20:25, 24 March 2013

OCA — Sun, 24 Mar 2013 20:25:24 GMT

←Older revision		Revision as of 20:25, 24 March 2013
Line 1:		Line 1:
-	[[Image:3sv1.jpg\|left\|200px]]
-
	{{STRUCTURE_3sv1\| PDB=3sv1 \| SCENE= }}		{{STRUCTURE_3sv1\| PDB=3sv1 \| SCENE= }}
-
	===Crystal structure of APP peptide bound rat Mint2 PARM===		===Crystal structure of APP peptide bound rat Mint2 PARM===
		+	{{ABSTRACT_PUBMED_22730553}}

-	~~{{ABSTRACT_PUBMED_22730553}}~~	+	==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:022730553</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022730553</ref><references group="xtra"/><references/>
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
	[[Category: Long, J.]]		[[Category: Long, J.]]

OCA at 08:08, 11 July 2012

OCA — Wed, 11 Jul 2012 08:08:16 GMT

←Older revision		Revision as of 08:08, 11 July 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3sv1.jpg\|left\|200px]]

-	~~The entry~~ 3sv1 ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_3sv1\| PDB=3sv1 \| SCENE= }}

-	~~Authors: Shen, Y., Long, J., Yan, X., Xie, X.~~	+	===Crystal structure of APP peptide bound rat Mint2 PARM===

-	~~Description: Crystal~~ structure ~~of APP peptide bound rat Mint2 PARM~~	+	{{ABSTRACT_PUBMED_22730553}}
		+
		+	==About this Structure==
		+	[[3sv1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SV1 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022730553</ref><references group="xtra"/>
		+	[[Category: Rattus norvegicus]]
		+	[[Category: Long, J.]]
		+	[[Category: Shen, Y.]]
		+	[[Category: Xie, X.]]
		+	[[Category: Yan, X.]]
		+	[[Category: App binding]]
		+	[[Category: Protein binding]]

OCA at 08:21, 3 August 2011

OCA — Wed, 03 Aug 2011 08:21:58 GMT

←Older revision		Revision as of 08:21, 3 August 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3sv1 is ON HOLD	+	The entry 3sv1 is ON HOLD until Paper Publication

-	Authors: ~~Yuequan~~ Shen, ~~Jiafu~~ Long, ~~Xiaojie~~ Yan, ~~Xingqiao~~ Xie	+	Authors: Shen, Y., Long, J., Yan, X., Xie, X.

-	Description: ~~crystal~~ structure of APP peptide bound rat Mint2 PARM	+	Description: Crystal structure of APP peptide bound rat Mint2 PARM

OCA: Protected "3sv1" [edit=sysop:move=sysop]

OCA — Wed, 20 Jul 2011 06:17:43 GMT

Protected "3sv1" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:17, 20 July 2011

OCA: New page: '''Unreleased structure''' The entry 3sv1 is ON HOLD Authors: Yuequan Shen, Jiafu Long, Xiaojie Yan, Xingqiao Xie Description: crystal structure of APP peptide bound rat Mint2 PARM

OCA — Wed, 20 Jul 2011 06:17:42 GMT

New page: '''Unreleased structure''' The entry 3sv1 is ON HOLD Authors: Yuequan Shen, Jiafu Long, Xiaojie Yan, Xingqiao Xie Description: crystal structure of APP peptide bound rat Mint2 PARM

New page

'''Unreleased structure'''

The entry 3sv1 is ON HOLD

Authors: Yuequan Shen, Jiafu Long, Xiaojie Yan, Xingqiao Xie

Description: crystal structure of APP peptide bound rat Mint2 PARM