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© The Rockefeller University Press, 0021-9525/2001//851 $5.00
The Journal of Cell Biology, Volume 152, Number 4, , 2001 851-856

An Essential Role for the Substrate-Binding Region of Hsp40s in Saccharomyces cerevisiae

^a Department of Biomolecular Chemistry, University of Wisconsin–Madison, Madison, Wisconson 53706
Department of Biomolecular Chemistry, University of Wisconsin–Madison, 1300 University Ave., Madison, WI 53706.(608) 262-5253(608) 263-7105

ecraig{at}facstaff.wisc.edu

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.

Key Words: Ydj1 • Sis1 • molecular chaperone • heat shock protein 70 • yeast

© 2001 The Rockefeller University Press

Abbreviations used in this paper: 5-FOA, 5-fluroorotic acid; a.a., amino acids; ALA, -aminolevulinic acid; G/F, glycine and phenylalanine residues.

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