Functionality of Class A and Class B J-protein co-chaperones with Hsp70

FEBS Lett. 2015 Sep 14;589(19 Pt B):2825-30. doi: 10.1016/j.febslet.2015.07.040. Epub 2015 Aug 3.


At their C-termini, cytosolic Hsp70s have an EEVD tetrapeptide that interacts with J-protein co-chaperones of the B, but not A, class. This interaction is required for partnering with yeast B-type J-proteins in protein folding. Here we report conservation of this feature. Human B-type J-proteins also have a stringent EEVD requirement. Human A-type J-proteins function less well than their yeast orthologs with Hsp70ΔEEVD. Changes in the zinc binding domain, a domain absent in B-type J-proteins, overcomes this partial EEVD dependence. Our results suggest that the structurally similar A- and B-class J-proteins of the cytosol have evolved conserved, yet distinct, features that enhance specialized functionality of Hsp70 machinery.

Keywords: EEVD motif; Hsp40; Hsp70; Molecular chaperone; Protein folding; Zinc binding domain.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Conserved Sequence
  • Cytosol / metabolism
  • HSP40 Heat-Shock Proteins / chemistry
  • HSP40 Heat-Shock Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Refolding
  • Protein Structure, Tertiary
  • Zinc / metabolism


  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Zinc