Insights into Hsp70 Chaperone Activity from a Crystal Structure of the Yeast Hsp110 Sse1

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2007 Oct 10

PMID 17923091

Citations 138

Authors

Qinglian Liu

Wayne A Hendrickson

Affiliations

Soon will be listed here.

Abstract

Classic Hsp70 chaperones assist in diverse processes of protein folding and translocation, and Hsp110s had seemed by sequence to be distant relatives within an Hsp70 superfamily. The 2.4 A resolution structure of Sse1 with ATP shows that Hsp110s are indeed Hsp70 relatives, and it provides insight into allosteric coupling between sites for ATP and polypeptide-substrate binding in Hsp70s. Subdomain structures are similar in intact Sse1(ATP) and in the separate Hsp70 domains, but conformational dispositions are radically different. Interfaces between Sse1 domains are extensive, intimate, and conservative in sequence with Hsp70s. We propose that Sse1(ATP) may be an evolutionary vestige of the Hsp70(ATP) state, and an analysis of 64 mutant variants in Sse1 and three Hsp70 homologs supports this hypothesis. An atomic-level understanding of Hsp70 communication between ATP and substrate-binding domains follows. Requirements on Sse1 for yeast viability are in keeping with the distinct function of Hsp110s as nucleotide exchange factors.

Citing Articles

Advances in the structures, mechanisms and targeting of molecular chaperones.

Gu J, He Y, He C, Zhang Q, Huang Q, Bai S Signal Transduct Target Ther. 2025; 10(1):84.

PMID: 40069202 PMC: 11897415. DOI: 10.1038/s41392-025-02166-2.

Early steps of protein disaggregation by Hsp70 chaperone and class B J-domain proteins are shaped by Hsp110.

Sztangierska W, Wyszkowski H, Pokornowska M, Kochanowicz K, Rychlowski M, Liberek K Elife. 2024; 13.

PMID: 39404743 PMC: 11479587. DOI: 10.7554/eLife.94795.

Sse1, Hsp110 chaperone of yeast, controls the cellular fate during endoplasmic reticulum stress.

Jha M, Kumar V, Ghosh A, Mapa K G3 (Bethesda). 2024; 14(6).

PMID: 38577891 PMC: 11152076. DOI: 10.1093/g3journal/jkae075.

Exploring the Role of the Plant Actin Cytoskeleton: From Signaling to Cellular Functions.

Yuan G, Gao H, Yang T Int J Mol Sci. 2023; 24(20).

PMID: 37895158 PMC: 10607326. DOI: 10.3390/ijms242015480.

Facing the phase problem.

Hendrickson W IUCrJ. 2023; 10(Pt 5):521-543.

PMID: 37668214 PMC: 10478523. DOI: 10.1107/S2052252523006449.

References

Moro F, Fernandez V, Muga A . Interdomain interaction through helices A and B of DnaK peptide binding domain. FEBS Lett. 2002; 533(1-3):119-23. DOI: 10.1016/s0014-5793(02)03752-3. View

Dragovic Z, Broadley S, Shomura Y, Bracher A, Hartl F . Molecular chaperones of the Hsp110 family act as nucleotide exchange factors of Hsp70s. EMBO J. 2006; 25(11):2519-28. PMC: 1478182. DOI: 10.1038/sj.emboj.7601138. View

Zhang Y, Zuiderweg E . The 70-kDa heat shock protein chaperone nucleotide-binding domain in solution unveiled as a molecular machine that can reorient its functional subdomains. Proc Natl Acad Sci U S A. 2004; 101(28):10272-7. PMC: 478562. DOI: 10.1073/pnas.0401313101. View

Wilbanks S, Chen L, Tsuruta H, Hodgson K, McKay D . Solution small-angle X-ray scattering study of the molecular chaperone Hsc70 and its subfragments. Biochemistry. 1995; 34(38):12095-106. DOI: 10.1021/bi00038a002. View

Shaner L, Trott A, Goeckeler J, Brodsky J, Morano K . The function of the yeast molecular chaperone Sse1 is mechanistically distinct from the closely related hsp70 family. J Biol Chem. 2004; 279(21):21992-2001. DOI: 10.1074/jbc.M313739200. View

Shaner L, Wegele H, Buchner J, Morano K . The yeast Hsp110 Sse1 functionally interacts with the Hsp70 chaperones Ssa and Ssb. J Biol Chem. 2005; 280(50):41262-9. DOI: 10.1074/jbc.M503614200. View

Sondermann H, Scheufler C, Schneider C, Hohfeld J, Hartl F, Moarefi I . Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science. 2001; 291(5508):1553-7. DOI: 10.1126/science.1057268. View

Raviol H, Bukau B, Mayer M . Human and yeast Hsp110 chaperones exhibit functional differences. FEBS Lett. 2005; 580(1):168-74. DOI: 10.1016/j.febslet.2005.11.069. View

Hesterkamp T, Bukau B . Role of the DnaK and HscA homologs of Hsp70 chaperones in protein folding in E.coli. EMBO J. 1998; 17(16):4818-28. PMC: 1170811. DOI: 10.1093/emboj/17.16.4818. View

10.

Swain J, Dinler G, Sivendran R, Montgomery D, Stotz M, Gierasch L . Hsp70 chaperone ligands control domain association via an allosteric mechanism mediated by the interdomain linker. Mol Cell. 2007; 26(1):27-39. PMC: 1894942. DOI: 10.1016/j.molcel.2007.02.020. View

11.

Liu Q, Krzewska J, Liberek K, Craig E . Mitochondrial Hsp70 Ssc1: role in protein folding. J Biol Chem. 2000; 276(9):6112-8. DOI: 10.1074/jbc.M009519200. View

12.

Burkholder W, Zhao X, Zhu X, Hendrickson W, Gragerov A, GOTTESMAN M . Mutations in the C-terminal fragment of DnaK affecting peptide binding. Proc Natl Acad Sci U S A. 1996; 93(20):10632-7. PMC: 38205. DOI: 10.1073/pnas.93.20.10632. View

13.

Revington M, Zhang Y, Yip G, Kurochkin A, Zuiderweg E . NMR investigations of allosteric processes in a two-domain Thermus thermophilus Hsp70 molecular chaperone. J Mol Biol. 2005; 349(1):163-83. DOI: 10.1016/j.jmb.2005.03.033. View

14.

Steel G, Fullerton D, Tyson J, Stirling C . Coordinated activation of Hsp70 chaperones. Science. 2004; 303(5654):98-101. DOI: 10.1126/science.1092287. View

15.

Li J, Wu Y, Qian X, Sha B . Crystal structure of yeast Sis1 peptide-binding fragment and Hsp70 Ssa1 C-terminal complex. Biochem J. 2006; 398(3):353-60. PMC: 1559466. DOI: 10.1042/BJ20060618. View

16.

Jiang J, Prasad K, Lafer E, Sousa R . Structural basis of interdomain communication in the Hsc70 chaperone. Mol Cell. 2005; 20(4):513-24. PMC: 4443753. DOI: 10.1016/j.molcel.2005.09.028. View

17.

Zhu X, Zhao X, Burkholder W, Gragerov A, Ogata C, GOTTESMAN M . Structural analysis of substrate binding by the molecular chaperone DnaK. Science. 1996; 272(5268):1606-14. PMC: 5629921. DOI: 10.1126/science.272.5268.1606. View

18.

Shaner L, Sousa R, Morano K . Characterization of Hsp70 binding and nucleotide exchange by the yeast Hsp110 chaperone Sse1. Biochemistry. 2006; 45(50):15075-84. PMC: 2676923. DOI: 10.1021/bi061279k. View

19.

Buchberger A, Theyssen H, Schroder H, McCarty J, Virgallita G, Milkereit P . Nucleotide-induced conformational changes in the ATPase and substrate binding domains of the DnaK chaperone provide evidence for interdomain communication. J Biol Chem. 1995; 270(28):16903-10. DOI: 10.1074/jbc.270.28.16903. View

20.

Yam A, Albanese V, Lin H, Frydman J . Hsp110 cooperates with different cytosolic HSP70 systems in a pathway for de novo folding. J Biol Chem. 2005; 280(50):41252-61. DOI: 10.1074/jbc.M503615200. View