View source for 5wbw


==Yeast Hsp104 fragment 1-360==
<StructureSection load='5wbw' size='340' side='right'caption='[[5wbw]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wbw]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WBW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WBW FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5wbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wbw OCA], [http://pdbe.org/5wbw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wbw RCSB], [http://www.ebi.ac.uk/pdbsum/5wbw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wbw ProSAT]</span></td></tr>
</table>
== 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>  
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== Publication Abstract from PubMed ==
The ring-forming Hsp104 ATPase cooperates with Hsp70 and Hsp40 molecular chaperones to rescue stress-damaged proteins from both amorphous and amyloid-forming aggregates. The ability to do so relies upon pore loops present in the first ATP-binding domain (AAA-1; loop-1 and loop-2 ) and in the second ATP-binding domain (AAA-2; loop-3) of Hsp104, which face the protein translocating channel and couple ATP-driven changes in pore loop conformation to substrate translocation. A hallmark of loop-1 and loop-3 is an invariable and mutational sensitive aromatic amino acid (Tyr(257) and Tyr(662)) involved in substrate binding. However, the role of conserved aliphatic residues (Lys(256), Lys(258), and Val(663)) flanking the pore loop tyrosines, and the function of loop-2 in protein disaggregation has not been investigated. Here we present the crystal structure of an N-terminal fragment of Saccharomyces cerevisiae Hsp104 exhibiting molecular interactions involving both AAA-1 pore loops, which resemble contacts with bound substrate. Corroborated by biochemical experiments and functional studies in yeast, we show that aliphatic residues flanking Tyr(257) and Tyr(662) are equally important for substrate interaction, and abolish Hsp104 function when mutated to glycine. Unexpectedly, we find that loop-2 is sensitive to aspartate substitutions that impair Hsp104 function and abolish protein disaggregation when loop-2 is replaced by four aspartate residues. Our observations suggest that Hsp104 pore loops have non-overlapping functions in protein disaggregation and together coordinate substrate binding, unfolding, and translocation through the Hsp104 hexamer.

Structural determinants for protein unfolding and translocation by the Hsp104 protein disaggregase.,Lee J, Sung N, Yeo L, Chang C, Lee S, Tsai FTF Biosci Rep. 2017 Dec 22;37(6). pii: BSR20171399. doi: 10.1042/BSR20171399. Print , 2017 Dec 22. PMID:29175998<ref>PMID:29175998</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5wbw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lee, S]]
[[Category: Atpase]]
[[Category: Chaperone]]