4xxd - Revision history

OCA at 07:51, 27 September 2023

OCA — Wed, 27 Sep 2023 07:51:45 GMT

←Older revision		Revision as of 07:51, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XXD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XXD FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [https://pdbe.org/4xxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [https://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd ProSAT]</span></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]] 2.41Å</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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [https://pdbe.org/4xxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [https://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 17:57, 26 April 2023

OCA — Wed, 26 Apr 2023 17:57:03 GMT

←Older revision		Revision as of 17:57, 26 April 2023
Line 3:		Line 3:
	<StructureSection load='4xxd' size='340' side='right'caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='4xxd' size='340' side='right'caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4XXD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XXD 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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [~~http~~://pdbe.org/4xxd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd ProSAT]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [https://pdbe.org/4xxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [https://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd 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/IGKC_HUMAN IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:[https://omim.org/entry/614102 614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.<ref>PMID:3931219</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/IGKC_HUMAN IGKC_HUMAN]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Crespi~~, G A.N~~]]	+	[[Category: Crespi GAN]]
-	[[Category: Hermans~~, S J~~]]	+	[[Category: Hermans SJ]]
-	[[Category: Miles~~, L A~~]]	+	[[Category: Miles LA]]
-	[[Category: Parker~~, M W]]~~	+	[[Category: Parker MW]]
-	~~[[Category: Amyloid-beta]]~~	+
-	~~[[Category: Fab]]~~	+
-	~~[[Category: Immune system~~]]	+

OCA at 07:40, 4 March 2020

OCA — Wed, 04 Mar 2020 07:40:07 GMT

←Older revision		Revision as of 07:40, 4 March 2020
Line 1:		Line 1:

	==Crystal Structure of mid-region amyloid beta capture by solanezumab==		==Crystal Structure of mid-region amyloid beta capture by solanezumab==
-	<StructureSection load='4xxd' size='340' side='right' caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>	+	<StructureSection load='4xxd' size='340' side='right'caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD FirstGlance]. <br>
Line 24:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Crespi, G A.N]]		[[Category: Crespi, G A.N]]
	[[Category: Hermans, S J]]		[[Category: Hermans, S J]]

OCA at 22:47, 15 November 2017

OCA — Wed, 15 Nov 2017 22:47:33 GMT

←Older revision		Revision as of 22:47, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='4xxd' size='340' side='right' caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='4xxd' size='340' side='right' caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xxd]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD 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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://pdbe.org/4xxd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd ProSAT]</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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://pdbe.org/4xxd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Crespi, G A.N]]		[[Category: Crespi, G A.N]]
	[[Category: Hermans, S J]]		[[Category: Hermans, S J]]

OCA at 13:28, 4 May 2017

OCA — Thu, 04 May 2017 13:28:02 GMT

←Older revision		Revision as of 13:28, 4 May 2017
Line 1:		Line 1:
		+
	==Crystal Structure of mid-region amyloid beta capture by solanezumab==		==Crystal Structure of mid-region amyloid beta capture by solanezumab==
	<StructureSection load='4xxd' size='340' side='right' caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='4xxd' size='340' side='right' caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4xxd]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xxd]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD 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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd 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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://pdbe.org/4xxd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd 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 4xxd" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:16, 29 July 2015

OCA — Wed, 29 Jul 2015 08:16:30 GMT

←Older revision		Revision as of 08:16, 29 July 2015
Line 5:		Line 5:
	</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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd 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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd PDBsum]</span></td></tr>
	</table>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:37, 30 April 2015

OCA — Thu, 30 Apr 2015 11:37:42 GMT

←Older revision		Revision as of 11:37, 30 April 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal Structure of mid-region amyloid beta capture by solanezumab==
		+	<StructureSection load='4xxd' size='340' side='right' caption='[[4xxd]], [[Resolution\|resolution]] 2.41Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4xxd]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XXD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD 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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Solanezumab (Eli Lilly) and crenezumab (Genentech) are the leading clinical antibodies targeting Amyloid-beta (Abeta) to be tested in multiple Phase III clinical trials for the prevention of Alzheimer's disease in at-risk individuals. Abeta capture by these clinical antibodies is explained here with the first reported mid-region Abeta-anti-Abeta complex crystal structure. Solanezumab accommodates a large Abeta epitope (960 A(2) buried interface over residues 16 to 26) that forms extensive contacts and hydrogen bonds to the antibody, largely via main-chain Abeta atoms and a deeply buried Phe19-Phe20 dipeptide core. The conformation of Abeta captured is an intermediate between observed sheet and helical forms with intramolecular hydrogen bonds stabilising residues 20-26 in a helical conformation. Remarkably, Abeta-binding residues are almost perfectly conserved in crenezumab. The structure explains the observed shared cross reactivity of solanezumab and crenezumab with proteins abundant in plasma that exhibit this Phe-Phe dipeptide.

-	~~The entry 4xxd is ON HOLD~~	+	Molecular basis for mid-region amyloid-beta capture by leading Alzheimer's disease immunotherapies.,Crespi GA, Hermans SJ, Parker MW, Miles LA Sci Rep. 2015 Apr 16;5:9649. doi: 10.1038/srep09649. PMID:25880481<ref>PMID:25880481</ref>

-	~~Authors: Hermans~~, S.J., Crespi, G.A.N~~., Parker, M.W., Miles, L.A.~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Fab complex with Amyloid-beta~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: Parker, M.W]]	+	__TOC__
-	[[Category: ~~Hermans, S.J~~]]	+	</StructureSection>
-	[[Category: ~~Crespi, G.A.N~~]]	+	[[Category: Crespi, G A.N]]
-	[[Category: ~~Miles, L.A~~]]	+	[[Category: Hermans, S J]]
		+	[[Category: Miles, L A]]
		+	[[Category: Parker, M W]]
		+	[[Category: Amyloid-beta]]
		+	[[Category: Fab]]
		+	[[Category: Immune system]]

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

OCA — Sat, 07 Feb 2015 14:57:12 GMT

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

←Older revision

Revision as of 14:57, 7 February 2015

OCA: New page: '''Unreleased structure''' The entry 4xxd is ON HOLD Authors: Hermans, S.J., Crespi, G.A.N., Parker, M.W., Miles, L.A. Description: Fab complex with Amyloid-beta [[Category: Unreleased...

OCA — Sat, 07 Feb 2015 14:57:11 GMT

New page: '''Unreleased structure''' The entry 4xxd is ON HOLD Authors: Hermans, S.J., Crespi, G.A.N., Parker, M.W., Miles, L.A. Description: Fab complex with Amyloid-beta [[Category: Unreleased...

New page

'''Unreleased structure'''

The entry 4xxd is ON HOLD

Authors: Hermans, S.J., Crespi, G.A.N., Parker, M.W., Miles, L.A.

Description: Fab complex with Amyloid-beta
[[Category: Unreleased Structures]]
[[Category: Parker, M.W]]
[[Category: Hermans, S.J]]
[[Category: Crespi, G.A.N]]
[[Category: Miles, L.A]]