Protein folding activity of Hsp70 is modified differentially by the hsp40 co-chaperones Sis1 and Ydj1

J Biol Chem. 1998 Oct 23;273(43):27824-30. doi: 10.1074/jbc.273.43.27824.


Specification of Hsp70 action in cellular protein metabolism may occur through the formation of specialized Hsp70:Hsp40 pairs. To test this model, we compared the ability of purified Sis1 and Ydj1 to regulate the ATPase and protein-folding activity of Hsp70 Ssa1 and Ssb1/2 proteins. Ydj1 and Sis1 could both functionally interact with Ssa1, but not the Ssb1/2 proteins, to refold luciferase. Interestingly, Ydj1:Ssa1 could promote up to four times more luciferase folding than Sis1:Ssa1. This functional difference was explored and could not be accounted for by differences in the ability of Sis1 and Ydj1 to regulate Ssa1 ATPase activity. Instead, differences in the chaperone function of Ydj1 and Sis1 were observed. Ydj1 was dramatically more effective than Sis1 at suppressing the thermally induced aggregation of luciferase. Paradoxically, Sis1 and Ydj1 could bind similar quantities of chemically denatured luciferase. The polypeptide binding domain of Sis1 was found to lie between residues 171-352 and correspond to its conserved carboxyl terminus. The conserved carboxyl terminus of Ydj1 is also known to participate in the binding of nonnative polypeptides. Thus, Ydj1 appears more efficient at assisting Ssa1 in folding luciferase because its contains a zinc finger-like region that is absent from Sis1. Ydj1 and Sis1 are structurally and functionally distinct Hsp40 proteins that can specify Ssa1 action by generating Hsp70:Hsp40 pairs that exhibit different chaperone activities.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Fungal Proteins / metabolism
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / metabolism*
  • Luciferases / metabolism
  • Protein Binding
  • Protein Folding*
  • Saccharomyces cerevisiae Proteins*


  • Fungal Proteins
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • SIS1 protein, S cerevisiae
  • SSB1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • YDJ1 protein, S cerevisiae
  • Luciferases
  • Adenosine Triphosphatases
  • SSA1 protein, S cerevisiae