4pwq - Revision history

OCA at 07:35, 8 February 2023

OCA — Wed, 08 Feb 2023 07:35:22 GMT

←Older revision		Revision as of 07:35, 8 February 2023
Line 3:		Line 3:
	<StructureSection load='4pwq' size='340' side='right'caption='[[4pwq]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4pwq' size='340' side='right'caption='[[4pwq]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4pwq]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4PWQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4pwq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PWQ FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APP, A4, AD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4pwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwq OCA], [https://pdbe.org/4pwq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pwq RCSB], [https://www.ebi.ac.uk/pdbsum/4pwq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pwq ProSAT]</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=4pwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwq OCA], [~~http~~://pdbe.org/4pwq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4pwq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4pwq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4pwq 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 ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dahms~~, S O~~]]	+	[[Category: Dahms SO]]
-	[[Category: Hoefgen, S]]	+	[[Category: Hoefgen S]]
-	[[Category: Than~~, M E]]~~	+	[[Category: Than ME]]
-	~~[[Category: Dimerization]]~~	+
-	~~[[Category: Heparin binding]]~~	+
-	~~[[Category: Heparin binding protein~~]]	+

OCA at 07:40, 17 April 2019

OCA — Wed, 17 Apr 2019 07:40:58 GMT

←Older revision		Revision as of 07:40, 17 April 2019
Line 1:		Line 1:

	==HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE E1-DOMAIN of THE AMYLOID PRECURSOR PROTEIN==		==HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE E1-DOMAIN of THE AMYLOID PRECURSOR PROTEIN==
-	<StructureSection load='4pwq' size='340' side='right' caption='[[4pwq]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='4pwq' size='340' side='right'caption='[[4pwq]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4pwq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PWQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4pwq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PWQ 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=4pwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwq OCA], [http://pdbe.org/4pwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pwq RCSB], [http://www.ebi.ac.uk/pdbsum/4pwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pwq ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APP, A4, AD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4pwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwq OCA], [http://pdbe.org/4pwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pwq RCSB], [http://www.ebi.ac.uk/pdbsum/4pwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pwq ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4pwq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4pwq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Amyloid precursor protein 3D structures\|Amyloid precursor protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Dahms, S O]]		[[Category: Dahms, S O]]
	[[Category: Hoefgen, S]]		[[Category: Hoefgen, S]]

OCA at 14:29, 11 August 2016

OCA — Thu, 11 Aug 2016 14:29:28 GMT

←Older revision		Revision as of 14:29, 11 August 2016
Line 1:		Line 1:
		+
	==HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE E1-DOMAIN of THE AMYLOID PRECURSOR PROTEIN==		==HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE E1-DOMAIN of THE AMYLOID PRECURSOR PROTEIN==
	<StructureSection load='4pwq' size='340' side='right' caption='[[4pwq]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4pwq' size='340' side='right' caption='[[4pwq]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4pwq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PWQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4pwq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PWQ 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=4pwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pwq RCSB], [http://www.ebi.ac.uk/pdbsum/4pwq 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=4pwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwq OCA], [http://pdbe.org/4pwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pwq RCSB], [http://www.ebi.ac.uk/pdbsum/4pwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pwq ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	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 4pwq" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:47, 7 February 2015

OCA — Sat, 07 Feb 2015 15:47:44 GMT

←Older revision		Revision as of 15:47, 7 February 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==HIGH-RESOLUTION CRYSTAL STRUCTURE OF THE E1-DOMAIN of THE AMYLOID PRECURSOR PROTEIN==
		+	<StructureSection load='4pwq' size='340' side='right' caption='[[4pwq]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4pwq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PWQ 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=4pwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pwq RCSB], [http://www.ebi.ac.uk/pdbsum/4pwq 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 amyloid precursor protein (APP) and its proteolytic cleavage product Abeta are widely believed to be central to the etiology of Alzheimer's disease (AD). APP and its family members are also essential for proper neuronal development and homeostasis. APP is located at the cell surface and within intracellular compartments, cellular regions that exhibit different pH values. The AD-associated amyloidogenic processing of APP is initiated predominantly in intracellular acidic compartments, whereas its non-amyloidogenic cleavage is initiated at the cell surface at slightly basic pH. We analyzed the influence of pH on the APP-E1 domain and found that its two constituting subdomains, GFLD and CuBD, interact with each other in a pH-dependent manner. Dynamic light scattering showed that APP-E1 represents a more open conformation at neutral pH and a more closed conformation at acidic pH. Analyzing a 1.4 A, high-resolution X-ray structure of E1 derived from merohedrally twinned crystals resulted in the identification of individual residues that are responsible for these pH-dependent interactions. Mutational studies and dynamic light scattering measurements further proved that specific hydrogen bonds between the two carboxylates of D177 and E87, as well as between N89 and H147, are major determinants of this pH-driven conformational switch in APP-E1. These findings show how APP can adopt different conformations depending on pH and suggest that the protein fulfils different functions at distinct localizations within the cell. Additionally, our data suggest a novel strategy for treating AD based on regulating the amyloidogenic processing of APP by the specific interruption of the interaction between the APP-E1 subdomains.

-	The ~~entry 4pwq is ON HOLD until Paper Publication~~	+	The Amyloid Precursor Protein Shows a pH-Dependent Conformational Switch in Its E1 Domain.,Hoefgen S, Dahms SO, Oertwig K, Than ME J Mol Biol. 2015 Jan 30;427(2):433-42. doi: 10.1016/j.jmb.2014.12.005. Epub 2014 , Dec 17. PMID:25528641<ref>PMID:25528641</ref>

-	~~Authors: Hoefgen~~, S.~~, Dahms,~~ S.~~O., Than, M.E~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: X-ray structure of a human heparin binding protein~~	+	== References ==
-	~~[[Category: Unreleased Structures]]~~	+	<references/>
-	[[Category: Dahms, S.O]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Dahms, S O]]
	[[Category: Hoefgen, S]]		[[Category: Hoefgen, S]]
-	[[Category: Than, M.E]]	+	[[Category: Than, M E]]
		+	[[Category: Dimerization]]
		+	[[Category: Heparin binding]]
		+	[[Category: Heparin binding protein]]

OCA at 15:17, 24 December 2014

OCA — Wed, 24 Dec 2014 15:17:15 GMT

←Older revision		Revision as of 15:17, 24 December 2014
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	Description: X-ray structure of a human heparin binding protein		Description: X-ray structure of a human heparin binding protein
		+	[[Category: Unreleased Structures]]
		+	[[Category: Dahms, S.O]]
		+	[[Category: Hoefgen, S]]
		+	[[Category: Than, M.E]]

OCA at 07:27, 23 April 2014

OCA — Wed, 23 Apr 2014 07:27:43 GMT

←Older revision		Revision as of 07:27, 23 April 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4pwq is ON HOLD	+	The entry 4pwq is ON HOLD until Paper Publication

	Authors: Hoefgen, S., Dahms, S.O., Than, M.E.		Authors: Hoefgen, S., Dahms, S.O., Than, M.E.

	Description: X-ray structure of a human heparin binding protein		Description: X-ray structure of a human heparin binding protein

OCA: Protected "4pwq" [edit=sysop:move=sysop]

OCA — Wed, 02 Apr 2014 08:34:11 GMT

Protected "4pwq" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:34, 2 April 2014

OCA: New page: '''Unreleased structure''' The entry 4pwq is ON HOLD Authors: Hoefgen, S., Dahms, S.O., Than, M.E. Description: X-ray structure of a human heparin binding protein

OCA — Wed, 02 Apr 2014 08:34:10 GMT

New page: '''Unreleased structure''' The entry 4pwq is ON HOLD Authors: Hoefgen, S., Dahms, S.O., Than, M.E. Description: X-ray structure of a human heparin binding protein

New page

'''Unreleased structure'''

The entry 4pwq is ON HOLD

Authors: Hoefgen, S., Dahms, S.O., Than, M.E.

Description: X-ray structure of a human heparin binding protein