| Structural highlights
Function
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+].[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25]
Publication Abstract from PubMed
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.
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[26]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ Moriyama H, Edskes HK, Wickner RB. [URE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p. Mol Cell Biol. 2000 Dec;20(23):8916-22. PMID:11073991
- ↑ Jung G, Masison DC. Guanidine hydrochloride inhibits Hsp104 activity in vivo: a possible explanation for its effect in curing yeast prions. Curr Microbiol. 2001 Jul;43(1):7-10. PMID:11375656 doi:http://dx.doi.org/10.1007/s002840010251
- ↑ Ferreira PC, Ness F, Edwards SR, Cox BS, Tuite MF. The elimination of the yeast [PSI+] prion by guanidine hydrochloride is the result of Hsp104 inactivation. Mol Microbiol. 2001 Jun;40(6):1357-69. PMID:11442834
- ↑ Ness F, Ferreira P, Cox BS, Tuite MF. Guanidine hydrochloride inhibits the generation of prion "seeds" but not prion protein aggregation in yeast. Mol Cell Biol. 2002 Aug;22(15):5593-605. PMID:12101251
- ↑ Kryndushkin DS, Alexandrov IM, Ter-Avanesyan MD, Kushnirov VV. Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104. J Biol Chem. 2003 Dec 5;278(49):49636-43. Epub 2003 Sep 24. PMID:14507919 doi:http://dx.doi.org/10.1074/jbc.M307996200
- ↑ Lum R, Tkach JM, Vierling E, Glover JR. Evidence for an unfolding/threading mechanism for protein disaggregation by Saccharomyces cerevisiae Hsp104. J Biol Chem. 2004 Jul 9;279(28):29139-46. Epub 2004 May 5. PMID:15128736 doi:http://dx.doi.org/10.1074/jbc.M403777200
- ↑ Shorter J, Lindquist S. Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science. 2004 Jun 18;304(5678):1793-7. Epub 2004 May 20. PMID:15155912 doi:http://dx.doi.org/10.1126/science.1098007
- ↑ Haslbeck M, Miess A, Stromer T, Walter S, Buchner J. Disassembling protein aggregates in the yeast cytosol. The cooperation of Hsp26 with Ssa1 and Hsp104. J Biol Chem. 2005 Jun 24;280(25):23861-8. Epub 2005 Apr 20. PMID:15843375 doi:http://dx.doi.org/M502697200
- ↑ Cashikar AG, Duennwald M, Lindquist SL. A chaperone pathway in protein disaggregation. Hsp26 alters the nature of protein aggregates to facilitate reactivation by Hsp104. J Biol Chem. 2005 Jun 24;280(25):23869-75. Epub 2005 Apr 20. PMID:15845535 doi:http://dx.doi.org/M502854200
- ↑ Sanchez Y, Taulien J, Borkovich KA, Lindquist S. Hsp104 is required for tolerance to many forms of stress. EMBO J. 1992 Jun;11(6):2357-64. PMID:1600951
- ↑ Narayanan S, Walter S, Reif B. Yeast prion-protein, sup35, fibril formation proceeds by addition and substraction of oligomers. Chembiochem. 2006 May;7(5):757-65. PMID:16570324 doi:http://dx.doi.org/10.1002/cbic.200500382
- ↑ Shorter J, Lindquist S. Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities. Mol Cell. 2006 Aug 4;23(3):425-38. PMID:16885031 doi:http://dx.doi.org/S1097-2765(06)00386-8
- ↑ Satpute-Krishnan P, Langseth SX, Serio TR. Hsp104-dependent remodeling of prion complexes mediates protein-only inheritance. PLoS Biol. 2007 Feb;5(2):e24. PMID:17253904 doi:http://dx.doi.org/06-PLBI-RA-1776R2
- ↑ Doyle SM, Shorter J, Zolkiewski M, Hoskins JR, Lindquist S, Wickner S. Asymmetric deceleration of ClpB or Hsp104 ATPase activity unleashes protein-remodeling activity. Nat Struct Mol Biol. 2007 Feb;14(2):114-22. Epub 2007 Jan 28. PMID:17259993 doi:http://dx.doi.org/nsmb1198
- ↑ Kurahashi H, Nakamura Y. Channel mutations in Hsp104 hexamer distinctively affect thermotolerance and prion-specific propagation. Mol Microbiol. 2007 Mar;63(6):1669-83. PMID:17367387 doi:http://dx.doi.org/MMI5629
- ↑ Schaupp A, Marcinowski M, Grimminger V, Bosl B, Walter S. Processing of proteins by the molecular chaperone Hsp104. J Mol Biol. 2007 Jul 20;370(4):674-86. Epub 2007 May 5. PMID:17543332 doi:http://dx.doi.org/S0022-2836(07)00583-9
- ↑ Tessarz P, Mogk A, Bukau B. Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation. Mol Microbiol. 2008 Apr;68(1):87-97. Epub 2008 Feb 28. PMID:18312264 doi:http://dx.doi.org/MMI6135
- ↑ Sanchez Y, Lindquist SL. HSP104 required for induced thermotolerance. Science. 1990 Jun 1;248(4959):1112-5. PMID:2188365
- ↑ Chernoff YO, Lindquist SL, Ono B, Inge-Vechtomov SG, Liebman SW. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science. 1995 May 12;268(5212):880-4. PMID:7754373
- ↑ Parsell DA, Kowal AS, Singer MA, Lindquist S. Protein disaggregation mediated by heat-shock protein Hsp104. Nature. 1994 Dec 1;372(6505):475-8. PMID:7984243 doi:http://dx.doi.org/10.1038/372475a0
- ↑ Sanchez Y, Parsell DA, Taulien J, Vogel JL, Craig EA, Lindquist S. Genetic evidence for a functional relationship between Hsp104 and Hsp70. J Bacteriol. 1993 Oct;175(20):6484-91. PMID:8407824
- ↑ Lindquist S, Kim G. Heat-shock protein 104 expression is sufficient for thermotolerance in yeast. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5301-6. PMID:8643570
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- ↑ Glover JR, Lindquist S. Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell. 1998 Jul 10;94(1):73-82. PMID:9674429
- ↑ 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. Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Science. 2017 Jul 21;357(6348):273-279. doi: 10.1126/science.aan1052. Epub 2017, Jun 15. PMID:28619716 doi:http://dx.doi.org/10.1126/science.aan1052
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