title: Functionality of Class A and Class B J-protein co-chaperones with Hsp70.
abstract: 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.
authors.affiliation: Department of Biochemistry, 433 Babcock Drive, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, 433 Babcock Drive, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ziegelhoffer
authors.affiliation: Department of Biochemistry, 433 Babcock Drive, University of Wisconsin - Madison, Madison, WI 53706, USA. Electronic address: ecraig@wisc.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Craig
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003600:Cytosol / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D058849:Protein Refolding; D017434:Protein Structure, Tertiary; D015032:Zinc / Q000378:metabolism
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D015032:Zinc
keywords: EEVD motif; Hsp40; Hsp70; Molecular chaperone; Protein folding; Zinc binding domain