Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity

Mol Cell. 2011 Mar 18;41(6):672-81. doi: 10.1016/j.molcel.2011.02.011.

Abstract

Heat shock protein 90 (Hsp90) is an essential molecular chaperone whose activity is regulated not only by cochaperones but also by distinct posttranslational modifications. We report here that casein kinase 2 phosphorylates a conserved threonine residue (T22) in α helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. This α helix participates in a hydrophobic interaction with the catalytic loop in Hsp90's middle domain, helping to stabilize the chaperone's ATPase-competent state. Phosphomimetic mutation of this residue alters Hsp90 ATPase activity and chaperone function and impacts interaction with the cochaperones Aha1 and Cdc37. Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chaperonins / chemistry
  • Chaperonins / genetics
  • Chaperonins / metabolism
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / chemistry*
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Phosphorylation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Threonine / metabolism*

Substances

  • AHA1 protein, S cerevisiae
  • CDC37 protein, S cerevisiae
  • Cell Cycle Proteins
  • Fungal Proteins
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Threonine
  • Casein Kinase II
  • Chaperonins