An essential role for the substrate-binding region of Hsp40s in Saccharomyces cerevisiae

J Cell Biol. 2001 Feb 19;152(4):851-6. doi: 10.1083/jcb.152.4.851.


In addition to regulating the ATPase cycle of Hsp70, a second critical role of Hsp40s has been proposed based on in vitro studies: binding to denatured protein substrates, followed by their presentation to Hsp70 for folding. However, the biological importance of this model is challenged by the fact that deletion of the substrate-binding domain of either of the two major Hsp40s of the yeast cytosol, Ydj1 and Sis1, leads to no severe defects, as long as regions necessary for Hsp70 interaction are retained. As an in vivo test of this model, requirements for viability were examined in a strain having deletions of both Hsp40 genes. Despite limited sequence similarity, the substrate-binding domain of either Sis1 or Ydj1 allowed cell growth, indicating they share overlapping essential functions. Furthermore, the substrate-binding domain must function in cis with a functional Hsp70-interacting domain. We conclude that the ability of cytosolic Hsp40s to bind unfolded protein substrates is an essential function in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Survival
  • Cytosol / metabolism
  • Gene Deletion
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins*


  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • SIS1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • YDJ1 protein, S cerevisiae