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7k3x

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<StructureSection load='7k3x' size='340' side='right'caption='[[7k3x]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
<StructureSection load='7k3x' size='340' side='right'caption='[[7k3x]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7k3x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K3X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K3X FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7k3x]] is a 1 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=7K3X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K3X FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7k3c|7k3c]]</div></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=7k3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k3x OCA], [https://pdbe.org/7k3x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k3x RCSB], [https://www.ebi.ac.uk/pdbsum/7k3x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k3x 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=7k3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k3x OCA], [https://pdbe.org/7k3x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k3x RCSB], [https://www.ebi.ac.uk/pdbsum/7k3x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k3x ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Disease ==
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== Publication Abstract from PubMed ==
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[[https://www.uniprot.org/uniprot/K2C8_HUMAN K2C8_HUMAN]] The disease is caused by variants affecting the gene represented in this entry.
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Proteins including FUS, hnRNPA2, and TDP-43 reversibly aggregate into amyloid-like fibrils through interactions of their low-complexity domains (LCDs). Mutations in LCDs can promote irreversible amyloid aggregation and disease. We introduce a computational approach to identify mutations in LCDs of disease-associated proteins predicted to increase propensity for amyloid aggregation. We identify several disease-related mutations in the intermediate filament protein keratin-8 (KRT8). Atomic structures of wild-type and mutant KRT8 segments confirm the transition to a pleated strand capable of amyloid formation. Biochemical analysis reveals KRT8 forms amyloid aggregates, and the identified mutations promote aggregation. Aggregated KRT8 is found in Mallory-Denk bodies, observed in hepatocytes of livers with alcoholic steatohepatitis (ASH). We demonstrate that ethanol promotes KRT8 aggregation, and KRT8 amyloids co-crystallize with alcohol. Lastly, KRT8 aggregation can be seeded by liver extract from people with ASH, consistent with the amyloid nature of KRT8 aggregates and the classification of ASH as an amyloid-related condition.
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== Function ==
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[[https://www.uniprot.org/uniprot/K2C8_HUMAN K2C8_HUMAN]] Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.<ref>PMID:16000376</ref>
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Identifying amyloid-related diseases by mapping mutations in low-complexity protein domains to pathologies.,Murray KA, Hughes MP, Hu CJ, Sawaya MR, Salwinski L, Pan H, French SW, Seidler PM, Eisenberg DS Nat Struct Mol Biol. 2022 May 30. pii: 10.1038/s41594-022-00774-y. doi:, 10.1038/s41594-022-00774-y. PMID:35637421<ref>PMID:35637421</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7k3x" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Eisenberg, D S]]
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[[Category: Eisenberg DS]]
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[[Category: Murray, K A]]
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[[Category: Murray KA]]
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[[Category: Sawaya, M R]]
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[[Category: Sawaya MR]]
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[[Category: Amyloid filament]]
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[[Category: Cryptogenic liver disease]]
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[[Category: Low complexity sequence]]
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[[Category: Protein fibril]]
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Revision as of 07:16, 8 September 2022

SGMGCIT segment 58-64 from Keratin-8 with G62C mutation

PDB ID 7k3x

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