OCA at 10:31, 24 November 2022

OCA — Thu, 24 Nov 2022 10:31:52 GMT

←Older revision		Revision as of 10:31, 24 November 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 8adw is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Lipidic alpha-synuclein fibril - polymorph L1C==
		+	<StructureSection load='8adw' size='340' side='right'caption='[[8adw]], [[Resolution\|resolution]] 2.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8adw]] is a 10 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=8ADW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ADW 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=8adw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8adw OCA], [https://pdbe.org/8adw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8adw RCSB], [https://www.ebi.ac.uk/pdbsum/8adw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8adw ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1. Defects in SNCA are the cause of Parkinson disease type 1 (PARK1) [MIM:[https://omim.org/entry/168601 168601]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.<ref>PMID:9197268</ref> <ref>PMID:9462735</ref> <ref>PMID:14755719</ref> Defects in SNCA are the cause of Parkinson disease type 4 (PARK4) [MIM:[https://omim.org/entry/605543 605543]. A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:[https://omim.org/entry/127750 127750]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	alpha-synuclein misfolding and aggregation into fibrils is a common feature of alpha-synucleinopathies, such as Parkinson's disease, in which alpha-synuclein fibrils are a characteristic hallmark of neuronal inclusions called Lewy bodies. Studies on the composition of Lewy bodies extracted postmortem from brain tissue of Parkinson's patients revealed that lipids and membranous organelles are also a significant component. Interactions between alpha-synuclein and lipids have been previously identified as relevant for Parkinson's disease pathology, however molecular insights into their interactions have remained elusive. Here we present cryo-electron microscopy structures of six alpha-synuclein fibrils in complex with lipids, revealing specific lipid-fibril interactions. We observe that phospholipids promote an alternative protofilament fold, mediate an unusual arrangement of protofilaments, and fill the central cavities of the fibrils. Together with our previous studies, these structures also indicate a mechanism for fibril-induced lipid extraction, which is likely to be involved in the development of alpha-synucleinopathies. Specifically, one potential mechanism for the cellular toxicity is the disruption of intracellular vesicles mediated by fibrils and oligomers, and therefore the modulation of these interactions may provide a promising strategy for future therapeutic interventions.

-	~~Authors~~:	+	The 3D structure of lipidic fibrils of alpha-synuclein.,Frieg B, Antonschmidt L, Dienemann C, Geraets JA, Najbauer EE, Matthes D, de Groot BL, Andreas LB, Becker S, Griesinger C, Schroder GF Nat Commun. 2022 Nov 10;13(1):6810. doi: 10.1038/s41467-022-34552-7. PMID:36357403<ref>PMID:36357403</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8adw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Andreas LB]]
		+	[[Category: Antonschmidt L]]
		+	[[Category: Becker S]]
		+	[[Category: Dienemann C]]
		+	[[Category: Frieg B]]
		+	[[Category: Geraets JA]]
		+	[[Category: Griesinger C]]
		+	[[Category: Matthes D]]
		+	[[Category: Najbauer EE]]
		+	[[Category: Schroeder GF]]
		+	[[Category: De Groot BL]]

OCA at 03:53, 10 August 2022

OCA — Wed, 10 Aug 2022 03:53:15 GMT

←Older revision		Revision as of 03:53, 10 August 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8adw is ON HOLD	+	The entry 8adw is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8adw" [edit=sysop:move=sysop]

OCA — Wed, 20 Jul 2022 04:15:53 GMT

Protected "8adw" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:15, 20 July 2022

OCA: New page: '''Unreleased structure''' The entry 8adw is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 20 Jul 2022 04:15:52 GMT

New page: '''Unreleased structure''' The entry 8adw is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8adw is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8adw - Revision history

OCA at 10:31, 24 November 2022

OCA at 03:53, 10 August 2022

OCA: Protected "8adw" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8adw is ON HOLD Authors: Description: Category: Unreleased Structures