OCA at 11:36, 26 August 2020

2020-08-26T11:36:31Z

←Older revision		Revision as of 11:36, 26 August 2020
Line 1:		Line 1:

	==X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid beta 16-36==		==X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid beta 16-36==
-	<StructureSection load='6wxm' size='340' side='right'caption='[[6wxm]]' scene=''>	+	<StructureSection load='6wxm' size='340' side='right'caption='[[6wxm]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WXM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WXM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6wxm]] is a 11 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WXM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WXM FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wxm OCA], [http://pdbe.org/6wxm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wxm RCSB], [http://www.ebi.ac.uk/pdbsum/6wxm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wxm ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene>, <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wxm OCA], [http://pdbe.org/6wxm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wxm RCSB], [http://www.ebi.ac.uk/pdbsum/6wxm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wxm ProSAT]</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;">
		+	== Publication Abstract from PubMed ==
		+	High-resolution structures of oligomers formed by the beta-amyloid peptide, Abeta, are important for understanding the molecular basis of Alzheimer's disease. Dimers of Abeta are linked to the pathogenesis and progression of Alzheimer's disease, and tetramers of Abeta are neurotoxic. This paper reports the X-ray crystallographic structures of dimers and tetramers, as well as an octamer, formed by a peptide derived from the central and C-terminal regions of Abeta. In the crystal lattice, the peptide assembles to form two different dimers-an antiparallel beta-sheet dimer and a parallel beta-sheet dimer-that each further self-assemble to form two different tetramers-a sandwich-like tetramer and a twisted beta-sheet tetramer. The structures of these dimers and tetramers derived from Abeta serve as potential models for dimers and tetramers of full-length Abeta that form in vitro and in Alzheimer's disease brains.
		+
		+	X-Ray Crystallography Reveals Parallel and Antiparallel beta-Sheet Dimers of a beta-Hairpin Derived from Abeta16-36 that Assemble to Form Different Tetramers.,Kreutzer AG, Samdin TD, Guaglianone G, Spencer RK, Nowick JS ACS Chem Neurosci. 2020 Jun 25. doi: 10.1021/acschemneuro.0c00290. PMID:32584538<ref>PMID:32584538</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6wxm" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kreutzer AG]]	+	[[Category: Kreutzer, A G]]
-	[[Category: Nowick JS]]	+	[[Category: Nowick, J S]]
		+	[[Category: Alzheimerss']]
		+	[[Category: De novo protein]]
		+	[[Category: Oligomer]]

OCA at 14:10, 8 July 2020

2020-07-08T14:10:13Z

←Older revision		Revision as of 14:10, 8 July 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6wxm is ON HOLD until Paper Publication~~	+	==X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid beta 16-36==
-		+	<StructureSection load='6wxm' size='340' side='right'caption='[[6wxm]]' scene=''>
-	~~Authors: Kreutzer, A.G., Nowick, J.S.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WXM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WXM FirstGlance]. <br>
-	~~Description:~~ X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid beta 16-36	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wxm OCA], [http://pdbe.org/6wxm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wxm RCSB], [http://www.ebi.ac.uk/pdbsum/6wxm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wxm ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Nowick~~, J.S]]	+	__TOC__
-	[[Category: Kreutzer~~, A.G~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Kreutzer AG]]
		+	[[Category: Nowick JS]]

OCA at 08:34, 17 June 2020

2020-06-17T08:34:32Z

←Older revision		Revision as of 08:34, 17 June 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6wxm is ON HOLD	+	The entry 6wxm is ON HOLD until Paper Publication

	Authors: Kreutzer, A.G., Nowick, J.S.		Authors: Kreutzer, A.G., Nowick, J.S.
Line 7:		Line 7:
	Description: X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid beta 16-36		Description: X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid beta 16-36
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Kreutzer, A.G]]
	[[Category: Nowick, J.S]]		[[Category: Nowick, J.S]]
		+	[[Category: Kreutzer, A.G]]

OCA: Protected "6wxm" [edit=sysop:move=sysop]

2020-05-20T04:19:51Z

Protected "6wxm" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:19, 20 May 2020

OCA: New page: '''Unreleased structure''' The entry 6wxm is ON HOLD Authors: Kreutzer, A.G., Nowick, J.S. Description: X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid ...

2020-05-20T04:19:49Z

New page: '''Unreleased structure''' The entry 6wxm is ON HOLD Authors: Kreutzer, A.G., Nowick, J.S. Description: X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid ...

New page

'''Unreleased structure'''

The entry 6wxm is ON HOLD

Authors: Kreutzer, A.G., Nowick, J.S.

Description: X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid beta 16-36
[[Category: Unreleased Structures]]
[[Category: Kreutzer, A.G]]
[[Category: Nowick, J.S]]

6wxm - Revision history

OCA at 11:36, 26 August 2020

OCA at 14:10, 8 July 2020

OCA at 08:34, 17 June 2020

OCA: Protected "6wxm" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6wxm is ON HOLD Authors: Kreutzer, A.G., Nowick, J.S. Description: X-ray crystallographic structure of a beta-hairpin peptide derived from amyloid ...