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| ==S. cerevisiae Hsp104:casein complex, Middle Domain Conformation== | | ==S. cerevisiae Hsp104:casein complex, Middle Domain Conformation== |
| <StructureSection load='5vy9' size='340' side='right' caption='[[5vy9]], [[Resolution|resolution]] 4.00Å' scene=''> | | <SX load='5vy9' size='340' side='right' viewer='molstar' caption='[[5vy9]], [[Resolution|resolution]] 6.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[5vy9]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VY9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VY9 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[5vy9]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VY9 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</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]] 6.7Å</td></tr> |
| <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene></td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vya|5vya]], [[5vy8|5vy8]], [[5vjh|5vjh]]</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=5vy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vy9 OCA], [https://pdbe.org/5vy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vy9 RCSB], [https://www.ebi.ac.uk/pdbsum/5vy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vy9 ProSAT]</span></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=5vy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vy9 OCA], [http://pdbe.org/5vy9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vy9 RCSB], [http://www.ebi.ac.uk/pdbsum/5vy9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vy9 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/HS104_YEAST HS104_YEAST]] Required, in concert with Hsp40 (YDJ1) and Hsp70 (SSA1) and small Hsps (HSP26), for the dissociation, resolubilization and refolding of aggregates of damaged proteins after heat or other environmental stresses. Extracts proteins from aggregates by unfolding and threading them in an ATP-dependent process through the axial channel of the protein hexamer, after which they can be refolded by components of the Hsp70/Hsp40 chaperone system. Substrate binding is ATP-dependent, and release of bound polypeptide is triggered by ATP hydrolysis. Also responsible for the maintenance of prions by dissociating prion fibrils into smaller oligomers, thereby producing transmissible seeds that can infect daughter cells during mitosis and meiosis. Loss of HSP104 can cure yeast cells of the prions [PSI+], [URE3] and [PIN+]. Excess HSP104 can also specifically cure cells of [PSI+].<ref>PMID:10678178</ref> <ref>PMID:11073991</ref> <ref>PMID:11375656</ref> <ref>PMID:11442834</ref> <ref>PMID:12101251</ref> <ref>PMID:14507919</ref> <ref>PMID:15128736</ref> <ref>PMID:15155912</ref> <ref>PMID:15843375</ref> <ref>PMID:15845535</ref> <ref>PMID:1600951</ref> <ref>PMID:16570324</ref> <ref>PMID:16885031</ref> <ref>PMID:17253904</ref> <ref>PMID:17259993</ref> <ref>PMID:17367387</ref> <ref>PMID:17543332</ref> <ref>PMID:18312264</ref> <ref>PMID:2188365</ref> <ref>PMID:7754373</ref> <ref>PMID:7984243</ref> <ref>PMID:8407824</ref> <ref>PMID:8643570</ref> <ref>PMID:9534180</ref> <ref>PMID:9674429</ref> | | [https://www.uniprot.org/uniprot/HS104_YEAST HS104_YEAST] Required, in concert with Hsp40 (YDJ1) and Hsp70 (SSA1) and small Hsps (HSP26), for the dissociation, resolubilization and refolding of aggregates of damaged proteins after heat or other environmental stresses. Extracts proteins from aggregates by unfolding and threading them in an ATP-dependent process through the axial channel of the protein hexamer, after which they can be refolded by components of the Hsp70/Hsp40 chaperone system. Substrate binding is ATP-dependent, and release of bound polypeptide is triggered by ATP hydrolysis. Also responsible for the maintenance of prions by dissociating prion fibrils into smaller oligomers, thereby producing transmissible seeds that can infect daughter cells during mitosis and meiosis. Loss of HSP104 can cure yeast cells of the prions [PSI+], [URE3] and [PIN+]. Excess HSP104 can also specifically cure cells of [PSI+].<ref>PMID:10678178</ref> <ref>PMID:11073991</ref> <ref>PMID:11375656</ref> <ref>PMID:11442834</ref> <ref>PMID:12101251</ref> <ref>PMID:14507919</ref> <ref>PMID:15128736</ref> <ref>PMID:15155912</ref> <ref>PMID:15843375</ref> <ref>PMID:15845535</ref> <ref>PMID:1600951</ref> <ref>PMID:16570324</ref> <ref>PMID:16885031</ref> <ref>PMID:17253904</ref> <ref>PMID:17259993</ref> <ref>PMID:17367387</ref> <ref>PMID:17543332</ref> <ref>PMID:18312264</ref> <ref>PMID:2188365</ref> <ref>PMID:7754373</ref> <ref>PMID:7984243</ref> <ref>PMID:8407824</ref> <ref>PMID:8643570</ref> <ref>PMID:9534180</ref> <ref>PMID:9674429</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from Saccharomyces cerevisiae solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo-electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions are mediated by conserved, pore-loop tyrosines that contact an 80-angstrom-long unfolded polypeptide along the axial channel. Two protomers undergo a ratchet-like conformational change that advances pore loop-substrate interactions by two amino acids. These changes are coupled to activation of specific nucleotide hydrolysis sites and, when transmitted around the hexamer, reveal a processive rotary translocation mechanism and substrate-responsive flexibility during Hsp104-catalyzed disaggregation.
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| Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104.,Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE, Sweeny EA, Mack KL, Chuang E, Torrente MP, Su M, Shorter J, Southworth DR Science. 2017 Jul 21;357(6348):273-279. doi: 10.1126/science.aan1052. Epub 2017, Jun 15. PMID:28619716<ref>PMID:28619716</ref>
| | ==See Also== |
| | | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| 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 5vy9" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </SX> |
| [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| [[Category: Buell, C E]] | | [[Category: Large Structures]] |
| [[Category: Chuang, E]] | | [[Category: Saccharomyces cerevisiae S288C]] |
| [[Category: Gates, S N]] | | [[Category: Buell CE]] |
| [[Category: Jackrel, M E]] | | [[Category: Chuang E]] |
| [[Category: Kendsersky, N M]] | | [[Category: Gates SN]] |
| [[Category: Lin, J B]] | | [[Category: Jackrel ME]] |
| [[Category: Mack, K L]] | | [[Category: Kendsersky NM]] |
| [[Category: Rizo, A N]] | | [[Category: Lin J-B]] |
| [[Category: Shorter, J]] | | [[Category: Mack KL]] |
| [[Category: Southworth, D R]] | | [[Category: Rizo AN]] |
| [[Category: Su, M]] | | [[Category: Shorter J]] |
| [[Category: Sweeny, E A]] | | [[Category: Southworth DR]] |
| [[Category: Torrente, M P]] | | [[Category: Su M]] |
| [[Category: Yokom, A L]] | | [[Category: Sweeny EA]] |
| [[Category: Aaa+]]
| | [[Category: Torrente MP]] |
| [[Category: Chaperone]]
| | [[Category: Yokom AL]] |
| [[Category: Cryoem]]
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| [[Category: Hsp104]]
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