OCA at 06:40, 29 March 2023

OCA — Wed, 29 Mar 2023 06:40:20 GMT

←Older revision		Revision as of 06:40, 29 March 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 7uak is ~~ON HOLD until Paper~~ Publication	+	==Structure of recombinantly assembled A53E alpha-synuclein fibrils==
		+	<StructureSection load='7uak' size='340' side='right'caption='[[7uak]], [[Resolution\|resolution]] 3.38Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7uak]] 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=7UAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UAK 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=7uak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uak OCA], [https://pdbe.org/7uak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uak RCSB], [https://www.ebi.ac.uk/pdbsum/7uak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uak ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple systems atrophy (MSA), have the same pathologic feature of misfolded alpha-synuclein protein (alpha-syn) accumulation in the brain. PD patients who carry alpha-syn hereditary mutations tend to have earlier onset and more severe clinical symptoms than sporadic PD patients who carry wild-type (WT) alpha-syn. Therefore, revealing the effect of hereditary mutations to the alpha-syn fibril structure can help us understand these synucleinopathies' structural basis. Here, we present a 3.38 A cryo-electron microscopy structure of alpha-synuclein fibrils containing the hereditary A53E mutation. The A53E fibril is symmetrically composed of two protofilaments, similar to other fibril structures of WT and mutant alpha-synuclein. The new structure is distinct from all other synuclein fibrils, not only at the interface between proto-filaments, but also between residues packed within the same proto-filament. Between the protofilaments, A53E has the smallest interface with the least buried surface area among all alpha-syn fibrils, consisting of only two contacting residues. Within the same protofilament, A53E reveals distinct residue re-arrangement and structural variation at a cavity near its fibril core. Moreover, the A53E fibrils exhibit slower fibril formation and lower stability compared to WT and other mutants like A53T and H50Q, while also demonstrate strong cellular seeding in alpha-synuclein biosensor cells and primary neurons. In summary, our study aims to highlight structural differences - both within and between the protofilaments of A53E fibrils - and interpret fibril formation and cellular seeding of alpha-synuclein pathology in disease, which could further our understanding of the structure-activity relationship of alpha-synuclein mutants.

-	~~Authors~~:	+	Cryo-EM structure of amyloid fibril formed by alpha-synuclein hereditary A53E mutation reveals a distinct protofilament interface.,Sun C, Zhou K, DePaola P 4th, Shin W, Hillyer T, Sawaya M, Zhu R, Peng C, Zhou ZH, Jiang L J Biol Chem. 2023 Mar 3:104566. doi: 10.1016/j.jbc.2023.104566. PMID:36871760<ref>PMID:36871760</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7uak" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Zhou H]]
		+	[[Category: Zhou K]]

OCA at 01:33, 21 April 2022

OCA — Thu, 21 Apr 2022 01:33:05 GMT

←Older revision		Revision as of 01:33, 21 April 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7uak is ON HOLD	+	The entry 7uak is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7uak" [edit=sysop:move=sysop]

OCA — Wed, 23 Mar 2022 09:50:27 GMT

Protected "7uak" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:50, 23 March 2022

OCA: New page: '''Unreleased structure''' The entry 7uak is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 23 Mar 2022 09:50:26 GMT

New page: '''Unreleased structure''' The entry 7uak is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7uak is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7uak - Revision history

OCA at 06:40, 29 March 2023

OCA at 01:33, 21 April 2022

OCA: Protected "7uak" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7uak is ON HOLD Authors: Description: Category: Unreleased Structures