View source for 7qwl


==TMEM106B filaments with Fold IIb from Multiple system atrophy (case 19)==
<StructureSection load='7qwl' size='340' side='right'caption='[[7qwl]], [[Resolution|resolution]] 3.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qwl]] is a 3 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=7QWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QWL 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=7qwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qwl OCA], [https://pdbe.org/7qwl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qwl RCSB], [https://www.ebi.ac.uk/pdbsum/7qwl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qwl 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>  
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== Publication Abstract from PubMed ==
Many age-dependent neurodegenerative diseases, like Alzheimer's and Parkinson's, are characterised by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-beta (Abeta), alpha-synuclein and TDP-43 are the most common(1,2). Here, we used electron cryo-microscopy (cryo-EM) structure determination to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brains. We determined the cryo-EM structures of TMEM106B filaments from a number of brain regions of 22 individuals with abundant amyloid deposits, including sporadic and inherited tauopathies, Abeta-amyloidoses, synucleinopathies and TDP-43 proteinopathies, as well as from the frontal cortex of 3 neurologically normal individuals with no or only few amyloid deposits. We observed three TMEM106B folds, with no clear relationships between folds and diseases. TMEM106B filaments correlated with the presence of a 29 kDa sarkosyl-insoluble fragment and globular cytoplasmic inclusions, as detected by an antibody specific for the C-terminal region of TMEM106B. The identification of TMEM106B filaments in the brains of older, but not younger, neurologically normal individuals indicates that they form in an age-dependent manner.

Age-dependent formation of TMEM106B amyloid filaments in human brains.,Schweighauser M, Arseni D, Bacioglu M, Huang M, Lovestam S, Shi Y, Yang Y, Zhang W, Kotecha A, Garringer HJ, Vidal R, Hallinan GI, Newell KL, Tarutani A, Murayama S, Miyazaki M, Saito Y, Yoshida M, Hasegawa K, Lashley T, Revesz T, Kovacs GG, van Swieten J, Takao M, Hasegawa M, Ghetti B, Spillantini MG, Ryskeldi-Falcon B, Murzin AG, Goedert M, Scheres SHW Nature. 2022 Mar 28. pii: 10.1038/s41586-022-04650-z. doi:, 10.1038/s41586-022-04650-z. PMID:35344985<ref>PMID:35344985</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qwl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lovestam, S]]
[[Category: Scheres, S H.W]]
[[Category: Schweighauser, M]]
[[Category: Amyloid]]
[[Category: Filament]]
[[Category: Neurodegeneration]]
[[Category: Protein fibril]]
[[Category: Tmem106b]]