View source for 7u12


==TMEM106B(120-254) singlet amyloid fibril from frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) type A (case 2)==
<StructureSection load='7u12' size='340' side='right'caption='[[7u12]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7u12]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U12 FirstGlance]. <br>
</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=7u12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u12 OCA], [https://pdbe.org/7u12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u12 RCSB], [https://www.ebi.ac.uk/pdbsum/7u12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u12 ProSAT]</span></td></tr>
</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 ==
Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or alpha-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 A from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration.

Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases.,Chang A, Xiang X, Wang J, Lee C, Arakhamia T, Simjanoska M, Wang C, Carlomagno Y, Zhang G, Dhingra S, Thierry M, Perneel J, Heeman B, Forgrave LM, DeTure M, DeMarco ML, Cook CN, Rademakers R, Dickson DW, Petrucelli L, Stowell MHB, Mackenzie IRA, Fitzpatrick AWP Cell. 2022 Mar 1. pii: S0092-8674(22)00259-8. doi: 10.1016/j.cell.2022.02.026. PMID:35247328<ref>PMID:35247328</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7u12" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Arakhamia, T]]
[[Category: Carlomagno, Y]]
[[Category: Chang, A]]
[[Category: Cook, C N]]
[[Category: DeMarco, M L]]
[[Category: DeTure, M]]
[[Category: Dhingra, S]]
[[Category: Dickson, D]]
[[Category: Fitzpatrick, A W.P]]
[[Category: Forgrave, L M]]
[[Category: Heeman, B]]
[[Category: Lee, C]]
[[Category: Mackenzie, I R.A]]
[[Category: Perneel, J]]
[[Category: Petrucelli, L]]
[[Category: Rademakers, R]]
[[Category: Simjanoska, M]]
[[Category: Stowell, M H.B]]
[[Category: Thierry, M]]
[[Category: Wang, C]]
[[Category: Wang, J]]
[[Category: Xiang, X]]
[[Category: Zhang, G]]
[[Category: Amyloid fibril]]
[[Category: Protein fibril]]
[[Category: Tmem106b]]