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| <StructureSection load='7saq' size='340' side='right'caption='[[7saq]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='7saq' size='340' side='right'caption='[[7saq]], [[Resolution|resolution]] 2.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7saq]] is a 5 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=7SAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SAQ FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SAQ 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> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9Å</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=7saq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7saq OCA], [https://pdbe.org/7saq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7saq RCSB], [https://www.ebi.ac.uk/pdbsum/7saq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7saq ProSAT]</span></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=7saq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7saq OCA], [https://pdbe.org/7saq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7saq RCSB], [https://www.ebi.ac.uk/pdbsum/7saq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7saq 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.
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| == 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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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7saq" style="background-color:#fffaf0;"></div>
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| == References ==
| |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Cao, Q]] | | [[Category: Cao Q]] |
| [[Category: Eisenberg, D S]] | | [[Category: Eisenberg DS]] |
| [[Category: Jiang, Y]] | | [[Category: Jiang Y]] |
| [[Category: Sawaya, M R]] | | [[Category: Sawaya MR]] |
| [[Category: Amyloid]]
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| [[Category: Ftld-tdp]]
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| [[Category: Protein fibril]]
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| [[Category: Tmem106b]]
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