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| <StructureSection load='6cew' size='340' side='right'caption='[[6cew]], [[Resolution|resolution]] 1.20Å' scene=''> | | <StructureSection load='6cew' size='340' side='right'caption='[[6cew]], [[Resolution|resolution]] 1.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6cew]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CEW FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6cew]] is a 2 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=6CEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CEW FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6cb9|6cb9]]</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cew OCA], [http://pdbe.org/6cew PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cew RCSB], [http://www.ebi.ac.uk/pdbsum/6cew PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cew 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=6cew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cew OCA], [https://pdbe.org/6cew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cew RCSB], [https://www.ebi.ac.uk/pdbsum/6cew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cew ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of beta-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible beta-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation.
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| Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.,Guenther EL, Cao Q, Trinh H, Lu J, Sawaya MR, Cascio D, Boyer DR, Rodriguez JA, Hughes MP, Eisenberg DS Nat Struct Mol Biol. 2018 May 21. pii: 10.1038/s41594-018-0064-2. doi:, 10.1038/s41594-018-0064-2. PMID:29786080<ref>PMID:29786080</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 6cew" style="background-color:#fffaf0;"></div>
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| == References ==
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| <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: Guenther, E L]] | | [[Category: Guenther EL]] |
| [[Category: Lu, J]] | | [[Category: Lu J]] |
| [[Category: Sawaya, M R]] | | [[Category: Sawaya MR]] |
| [[Category: Amyloid]]
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| [[Category: Protein fibril]]
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| [[Category: Steric-zipper]]
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