OCA at 13:07, 4 May 2022

OCA — Wed, 04 May 2022 13:07:39 GMT

←Older revision		Revision as of 13:07, 4 May 2022
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	==Cryo-EM structure of TMEM106B fibrils extracted from a FTLD-TDP patient, polymorph 2==		==Cryo-EM structure of TMEM106B fibrils extracted from a FTLD-TDP patient, polymorph 2==
-	<StructureSection load='7sar' size='340' side='right'caption='[[7sar]]' scene=''>	+	<StructureSection load='7sar' size='340' side='right'caption='[[7sar]], [[Resolution\|resolution]] 3.20Å' 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=7SAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SAR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7sar]] 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=7SAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SAR 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=7sar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sar OCA], [https://pdbe.org/7sar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sar RCSB], [https://www.ebi.ac.uk/pdbsum/7sar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sar 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7sar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sar OCA], [https://pdbe.org/7sar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sar RCSB], [https://www.ebi.ac.uk/pdbsum/7sar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sar ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/T106B_HUMAN T106B_HUMAN]] Progressive non-fluent aphasia;Semantic dementia;Behavioral variant of frontotemporal dementia. The gene represented in this entry acts as a disease modifier. Risk alleles confer genetic susceptibility by increasing gene expression (PubMed:20154673, PubMed:21178100). Increased expression may be the result of down-regulation of microRNA miR-132 and miR-212, that repress TMEM106B expression (PubMed:22895706). Thr-185 is a risk allele associated with lower GRN protein levels and early age at onset in GRN UP-FTD mutation carriers: it presents slower protein degradation that leads to higher steady-state TMEM106B levels, leading to alterations in the intracellular versus extracellular partitioning of GRN (PubMed:23742080).<ref>PMID:20154673</ref> <ref>PMID:21178100</ref> <ref>PMID:22895706</ref> <ref>PMID:23742080</ref> The gene represented in this entry acts as a disease modifier. The disease may be caused by variants affecting the gene represented in this entry.
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/T106B_HUMAN T106B_HUMAN]] Involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with MAP6. May act by inhibiting retrograde transport of lysosomes along dendrites. Required for dendrite branching.<ref>PMID:23136129</ref> <ref>PMID:24357581</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition, following only Alzheimer's and Parkinson's diseases(1). FTLD typically presents in 45-64-year-olds with behavioral changes or progressive decline of language skills(2). The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions detected by TAR DNA-binding protein (TDP-43) immunoreactivity(3). Here, we extracted amyloid fibrils from brains of four patients, representing four out of five FTLD-TDP subclasses and determined their near-atomic resolution structures by cryogenic electron-microscopy (cryo-EM). Unexpectedly, all amyloid fibrils examined are composed of a 135-residue C-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP(4). In addition to TMEM106B fibrils, abundant non-fibrillar aggregated TDP-43 is present, as revealed by immunogold labeling. Our observations confirm that FTLD-TDP is an amyloid-involved disease and suggest that amyloid involvement in FTLD-TDP is of protein TMEM106B, rather than of TDP-43.
		+
		+	Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43.,Jiang YX, Cao Q, Sawaya MR, Abskharon R, Ge P, DeTure M, Dickson DW, Fu JY, Ogorzalek Loo RR, Loo JA, Eisenberg DS Nature. 2022 Mar 28. pii: 10.1038/s41586-022-04670-9. doi:, 10.1038/s41586-022-04670-9. PMID:35344984<ref>PMID:35344984</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7sar" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cao Q]]	+	[[Category: Cao, Q]]
-	[[Category: Eisenberg DS]]	+	[[Category: Eisenberg, D S]]
-	[[Category: Jiang Y]]	+	[[Category: Jiang, Y]]
-	[[Category: Sawaya MR]]	+	[[Category: Sawaya, M R]]
		+	[[Category: Amyloid]]
		+	[[Category: Ftld-tdp]]
		+	[[Category: Protein fibril]]
		+	[[Category: Tmem106b]]

OCA at 06:07, 9 March 2022

OCA — Wed, 09 Mar 2022 06:07:31 GMT

←Older revision		Revision as of 06:07, 9 March 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7sar is ~~ON HOLD until Paper Publication~~	+	==Cryo-EM structure of TMEM106B fibrils extracted from a FTLD-TDP patient, polymorph 2==
-		+	<StructureSection load='7sar' size='340' side='right'caption='[[7sar]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SAR FirstGlance]. <br>
-	~~Description~~:	+	</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=7sar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sar OCA], [https://pdbe.org/7sar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sar RCSB], [https://www.ebi.ac.uk/pdbsum/7sar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sar ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Cao Q]]
		+	[[Category: Eisenberg DS]]
		+	[[Category: Jiang Y]]
		+	[[Category: Sawaya MR]]

OCA at 12:41, 27 October 2021

OCA — Wed, 27 Oct 2021 12:41:58 GMT

←Older revision		Revision as of 12:41, 27 October 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 29 Sep 2021 07:50:56 GMT

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

←Older revision

Revision as of 07:50, 29 September 2021

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

OCA — Wed, 29 Sep 2021 07:50:55 GMT

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

New page

'''Unreleased structure'''

The entry 7sar is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7sar - Revision history

OCA at 13:07, 4 May 2022

OCA at 06:07, 9 March 2022

OCA at 12:41, 27 October 2021

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

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