Skip to main content
SpringerLink
Log in
Book cover

Heat Shock Protein 90 in Human Diseases and Disorders pp 371–384Cite as

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

  • Chapter
  • First Online:

Part of the book series: Heat Shock Proteins ((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.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

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

References

  • Ali MM, Roe SM, Vaughan CK et al (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440:1013–1017

    Article  CAS  Google Scholar 

  • 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 27:3594–3607

    Article  CAS  Google Scholar 

  • 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 279:16185–16193

    Article  CAS  Google Scholar 

  • Chang HC, Nathan DF, Lindquist S (1997) In vivo analysis of the Hsp90 cochaperone Sti1 (p60). Mol Cell Biol 17:318–325

    Article  CAS  Google Scholar 

  • 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 10:682–693

    CAS  PubMed  Google Scholar 

  • 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 172:41–51

    Article  CAS  Google Scholar 

  • 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 404:159–167

    Article  CAS  Google Scholar 

  • 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 391:621–634

    Article  CAS  Google Scholar 

  • 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 49:464–473

    Article  CAS  Google Scholar 

  • 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 427:3877–3889

    Article  CAS  Google Scholar 

  • Jiang L, Mishra P, Hietpas RT, Zeldovich KB, Bolon DN (2013) Latent effects of Hsp90 mutants revealed at reduced expression levels. PLoS Genet 9:e1003600

    Article  CAS  Google Scholar 

  • 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 56:31–37

    Article  CAS  Google Scholar 

  • 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 24:3928–3937

    Article  CAS  Google Scholar 

  • Karagoz GE, Rudiger SG (2015) Hsp90 interaction with clients. Trends Biochem Sci 40:117–125

    Article  CAS  Google Scholar 

  • 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–E2E19

    Article  CAS  Google Scholar 

  • 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 18:1815–1827

    Article  CAS  Google Scholar 

  • Lee CT, Graf C, Mayer FJ, Richter SM, Mayer MP (2012) Dynamics of the regulation of Hsp90 by the co-chaperone Sti1. EMBO J 31:1518–1528

    Article  CAS  Google Scholar 

  • 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 4:849–860

    Article  CAS  Google Scholar 

  • 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 79:1581–1588

    Article  CAS  Google Scholar 

  • 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:e1000323

    Article  Google Scholar 

  • 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 34:783–785

    Article  CAS  Google Scholar 

  • Pratt WB, Morishima Y, Murphy M, Harrell M (2006) Chaperoning of glucocorticoid receptors. Handb Exp Pharmacol 172:111–138

    Article  CAS  Google Scholar 

  • Prodromou C (2016) Mechanisms of Hsp90 regulation. Biochem J 473:2439–2452

    Article  CAS  Google Scholar 

  • 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 19:4383–4392

    Article  CAS  Google Scholar 

  • Reidy M, Kumar S, Anderson DE, Masison DC (2018) Dual roles for yeast Sti1/Hop in regulating the Hsp90 chaperone cycle. Genetics 209:1139–1154

    Article  CAS  Google Scholar 

  • Retzlaff M, Stahl M, Eberl HC et al (2009) Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Rep 10:1147–1153

    Article  CAS  Google Scholar 

  • Retzlaff M, Hagn F, Mitschke L et al (2010) Asymmetric activation of the hsp90 dimer by its cochaperone aha1. Mol Cell 37:344–354

    Article  CAS  Google Scholar 

  • 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 6:6655

    Article  Google Scholar 

  • 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 101:199–210

    Article  CAS  Google Scholar 

  • Schmid AB, Lagleder S, Grawert MA et al (2012) The architecture of functional modules in the Hsp90 co-chaperone Sti1/Hop. EMBO J 31:1506–1517

    Article  CAS  Google Scholar 

  • Schopf FH, Biebl MM, Buchner J (2017) The HSP90 chaperone machinery. Nat Rev Mol Cell Biol 18:345–360

    Article  CAS  Google Scholar 

  • Song Y, Masison DC (2005) Independent regulation of Hsp70 and Hsp90 chaperones by Hsp70/Hsp90-organizing protein Sti1 (Hop1). J Biol Chem 280:34178–34185

    Article  CAS  Google Scholar 

  • 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 390:604–617

    Article  CAS  Google Scholar 

  • 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 42:771–781

    Article  CAS  Google Scholar 

  • Vaughan CK, Piper PW, Pearl LH, Prodromou C (2009) A common conformationally coupled ATPase mechanism for yeast and human cytoplasmic HSP90s. FEBS J 276:199–209

    Article  CAS  Google Scholar 

  • 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 352:1542–1547

    Article  CAS  Google Scholar 

  • Zuehlke AD, Johnson JL (2012) Chaperoning the chaperone: a role for the co-chaperone Cpr7 in modulating Hsp90 function in Saccharomyces cerevisiae. Genetics 191:805–814

    Article  CAS  Google Scholar 

  • 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 8:15328

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Michael Reidy

Authors
  1. Michael Reidy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Reidy .

Editor information

Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Reidy, M. (2019). Sti1/Hop Plays a Pivotal Role in Hsp90 Regulation Beyond Bridging Hsp70. In: Asea, A., Kaur, P. (eds) Heat Shock Protein 90 in Human Diseases and Disorders. Heat Shock Proteins, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_17

Download citation

Publish with us

Policies and ethics

Search

Navigation