Advertisement

Sti1/Hop Plays a Pivotal Role in Hsp90 Regulation Beyond Bridging Hsp70

  • Michael ReidyEmail author
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 19)

Abstract

Since its initial characterization, Hop (Hsp90/Hsp70 organizing protein), known as Sti1 in yeast (stress inducible) is mostly understood to serve as a bridge that facilitates transfer of substrate “client” proteins from Hsp70 to Hsp90. Recent work has shown that Sti1 regulates Hsp90 in a manner distinct from its role as a bridge to Hsp70. This second function of Sti1 seems to be to position Hsp90 for subsequent steps of the client maturation cycle, after the client has been transferred from Hsp70. Thus, Sti1/Hop occupies a central gatekeeper role in the Hsp90 reaction cycle, by first facilitating client access to Hsp90 and then promoting the next steps of the cycle.

Keywords

Chaperone Co-chaperone Hop Hsp Hsp70 Hsp90 Sti1 

Abbreviations

3D

Three dimensional

AR

Androgen receptor

ATP

Adenosine triphosphate

cryoEM

Cryoelectron microscopy

DP

Aspartate/proline-rich motif

EM

Electron microscopy

FOA

5′Fluoro-orotic acid

GR

Glucocorticoid receptor

Hop

Hsp90/Hsp70 organizing protein

Hsp

Heat shock protein

MAP

Mitogen-activated protein

SdC

Sti1-dependent carboxy-terminal proximal

SdN

Sti1-dependent amino-terminal proximal

TPR

Tetratricopeptide repeat

Notes

Acknowledgements

We thank our National Institutes of Health colleagues for insightful discussions and help with the manuscript. This work was supported by the Intramural Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney diseases.

References

  1. Ali MM, Roe SM, Vaughan CK et al (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440:1013–1017CrossRefGoogle Scholar
  2. Beraldo FH, Soares IN, Goncalves DF et al (2013) Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein. FASEB J 27:3594–3607CrossRefGoogle Scholar
  3. Carrigan PE, Nelson GM, Roberts PJ, Stoffer J, Riggs DL, Smith DF (2004) Multiple domains of the co-chaperone Hop are important for Hsp70 binding. J Biol Chem 279:16185–16193CrossRefGoogle Scholar
  4. Chang HC, Nathan DF, Lindquist S (1997) In vivo analysis of the Hsp90 cochaperone Sti1 (p60). Mol Cell Biol 17:318–325CrossRefGoogle Scholar
  5. Chen S, Prapapanich V, Rimerman RA, Honore B, Smith DF (1996) Interactions of p60, a mediator of progesterone receptor assembly, with heat shock proteins hsp90 and hsp70. Mol Endocrinol 10:682–693PubMedGoogle Scholar
  6. Flom G, Weekes J, Williams JJ, Johnson JL (2006) Effect of mutation of the tetratricopeptide repeat and asparatate-proline 2 domains of Sti1 on Hsp90 signaling and interaction in Saccharomyces cerevisiae. Genetics 172:41–51CrossRefGoogle Scholar
  7. Flom G, Behal RH, Rosen L, Cole DG, Johnson JL (2007) Definition of the minimal fragments of Sti1 required for dimerization, interaction with Hsp70 and Hsp90 and in vivo functions. Biochem J 404:159–167CrossRefGoogle Scholar
  8. Gaiser AM, Brandt F, Richter K (2009) The non-canonical Hop protein from Caenorhabditis elegans exerts essential functions and forms binary complexes with either Hsc70 or Hsp90. J Mol Biol 391:621–634CrossRefGoogle Scholar
  9. Genest O, Reidy M, Street TO et al (2013) Uncovering a region of heat shock protein 90 important for client binding in E. coli and chaperone function in yeast. Mol Cell 49:464–473CrossRefGoogle Scholar
  10. Genest O, Hoskins JR, Kravats AN, Doyle SM, Wickner S (2015) Hsp70 and Hsp90 of E. coli directly interact for collaboration in protein remodeling. J Mol Biol 427:3877–3889CrossRefGoogle Scholar
  11. Jiang L, Mishra P, Hietpas RT, Zeldovich KB, Bolon DN (2013) Latent effects of Hsp90 mutants revealed at reduced expression levels. PLoS Genet 9:e1003600CrossRefGoogle Scholar
  12. Johnson J, Corbisier R, Stensgard B, Toft D (1996) The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes. J Steroid Biochem Mol Biol 56:31–37CrossRefGoogle Scholar
  13. Jones G, Song Y, Chung S, Masison DC (2004) Propagation of Saccharomyces cerevisiae [PSI+] prion is impaired by factors that regulate Hsp70 substrate binding. Mol Cell Biol 24:3928–3937CrossRefGoogle Scholar
  14. Karagoz GE, Rudiger SG (2015) Hsp90 interaction with clients. Trends Biochem Sci 40:117–125CrossRefGoogle Scholar
  15. Kravats AN, Hoskins JR, Reidy M et al (2018) Functional and physical interaction between yeast Hsp90 and Hsp70. Proc Natl Acad Sci U S A 115:E2210–E2E19CrossRefGoogle Scholar
  16. Krukenberg KA, Bottcher UM, Southworth DR, Agard DA (2009) Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide. Protein Sci 18:1815–1827CrossRefGoogle Scholar
  17. Lee CT, Graf C, Mayer FJ, Richter SM, Mayer MP (2012) Dynamics of the regulation of Hsp90 by the co-chaperone Sti1. EMBO J 31:1518–1528CrossRefGoogle Scholar
  18. Millson SH, Truman AW, King V, Prodromou C, Pearl LH, Piper PW (2005) A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p). Eukaryot Cell 4:849–860CrossRefGoogle Scholar
  19. Millson SH, Prodromou C, Piper PW (2010) A simple yeast-based system for analyzing inhibitor resistance in the human cancer drug targets Hsp90alpha/beta. Biochem Pharmacol 79:1581–1588CrossRefGoogle Scholar
  20. Morra G, Verkhivker G, Colombo G (2009) Modeling signal propagation mechanisms and ligand-based conformational dynamics of the Hsp90 molecular chaperone full-length dimer. PLoS Comput Biol 5:e1000323CrossRefGoogle Scholar
  21. Piper PW, Truman AW, Millson SH, Nuttall J (2006) Hsp90 chaperone control over transcriptional regulation by the yeast Slt2(Mpk1)p and human ERK5 mitogen-activated protein kinases (MAPKs). Biochem Soc Trans 34:783–785CrossRefGoogle Scholar
  22. Pratt WB, Morishima Y, Murphy M, Harrell M (2006) Chaperoning of glucocorticoid receptors. Handb Exp Pharmacol 172:111–138CrossRefGoogle Scholar
  23. Prodromou C (2016) Mechanisms of Hsp90 regulation. Biochem J 473:2439–2452CrossRefGoogle Scholar
  24. Prodromou C, Panaretou B, Chohan S et al (2000) The ATPase cycle of Hsp90 drives a molecular ‘clamp’ via transient dimerization of the N-terminal domains. EMBO J 19:4383–4392CrossRefGoogle Scholar
  25. Reidy M, Kumar S, Anderson DE, Masison DC (2018) Dual roles for yeast Sti1/Hop in regulating the Hsp90 chaperone cycle. Genetics 209:1139–1154CrossRefGoogle Scholar
  26. Retzlaff M, Stahl M, Eberl HC et al (2009) Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Rep 10:1147–1153CrossRefGoogle Scholar
  27. Retzlaff M, Hagn F, Mitschke L et al (2010) Asymmetric activation of the hsp90 dimer by its cochaperone aha1. Mol Cell 37:344–354CrossRefGoogle Scholar
  28. Rohl A, Wengler D, Madl T et al (2015) Hsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70 between modules. Nat Commun 6:6655CrossRefGoogle Scholar
  29. Scheufler C, Brinker A, Bourenkov G et al (2000) Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 101:199–210CrossRefGoogle Scholar
  30. Schmid AB, Lagleder S, Grawert MA et al (2012) The architecture of functional modules in the Hsp90 co-chaperone Sti1/Hop. EMBO J 31:1506–1517CrossRefGoogle Scholar
  31. Schopf FH, Biebl MM, Buchner J (2017) The HSP90 chaperone machinery. Nat Rev Mol Cell Biol 18:345–360CrossRefGoogle Scholar
  32. Song Y, Masison DC (2005) Independent regulation of Hsp70 and Hsp90 chaperones by Hsp70/Hsp90-organizing protein Sti1 (Hop1). J Biol Chem 280:34178–34185CrossRefGoogle Scholar
  33. Song HO, Lee W, An K et al (2009) C. elegans STI-1, the homolog of Sti1/Hop, is involved in aging and stress response. J Mol Biol 390:604–617CrossRefGoogle Scholar
  34. Southworth DR, Agard DA (2011) Client-loading conformation of the Hsp90 molecular chaperone revealed in the cryo-EM structure of the human Hsp90:Hop complex. Mol Cell 42:771–781CrossRefGoogle Scholar
  35. Vaughan CK, Piper PW, Pearl LH, Prodromou C (2009) A common conformationally coupled ATPase mechanism for yeast and human cytoplasmic HSP90s. FEBS J 276:199–209CrossRefGoogle Scholar
  36. Verba KA, Wang RY, Arakawa A et al (2016) Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase. Science 352:1542–1547CrossRefGoogle Scholar
  37. Zuehlke AD, Johnson JL (2012) Chaperoning the chaperone: a role for the co-chaperone Cpr7 in modulating Hsp90 function in Saccharomyces cerevisiae. Genetics 191:805–814CrossRefGoogle Scholar
  38. Zuehlke AD, Reidy M, Lin C et al (2017) An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans. Nat Commun 8:15328CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Laboratory of Biochemistry and GeneticsNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesdaUSA

Personalised recommendations