Genetics. Published Articles Ahead of Print: November 19, 2005, Copyright © 2005
doi:10.1534/genetics.105.048926


A more recent version of this article appeared on February 1, 2006.

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Primate chaperones Hsc70 (constitutive) and Hsp70 (induced) differ functionally in supporting growth and prion propagation in Saccharomyces cerevisiae

Yusuf Tutar 1, Youtao Song 2 and Daniel C. Masison 3*

1 Cumhuriyet University
2 Liaoning University
3 National Institutes of Health

* To whom correspondence should be addressed. E-mail: masisond{at}helix.nih.gov.

Submitted on July 28, 2005
Revised on October 11, 2005
Accepted on 24 October 2005


Abstract

Hsp70s are highly conserved essential protein chaperones that assist protein folding and prevent protein aggregation. They have modular structures consisting of ATPase, substrate-binding and C-terminal domains. Substrate binding and release is regulated by ATP hydrolysis and nucleotide exchange, which in turn are regulated by co-chaperones. Eukaryotes have constitutive (Hsc70) and stress-inducible (iHsp70) isoforms, but their functions have not been systematically compared. Using a yeast system to evaluate heterologous Hsp70s we find primate Hsc70 supported growth but iHsp70 did not. Plant Hsc70 and iHsp70 counterparts behaved similarly, implying evolutionary conservation of this distinction. Swapping yeast and primate Hsp70 domains showed (i) the Hsc70-iHsp70 distinction resided in the ATPase domain, (ii) substrate-binding domains of Hsp70s within and across species functioned similarly regarding growth, (iii) C-terminal domain function was important for growth, and (iv) Hsp70 functions important for cell growth and prion propagation were separable. Enzymatic analysis uncovered a correlation between substrate affinity and prion phenotype and showed that ATPase and protein folding activities were generally similar. Our data support a view that intrinsic activities of Hsp70 isoforms are comparable, and functional differences in vivo lie mainly in complex interactions of Hsp70 with co-chaperones.

Key Words: Hsc70, Hsp70, prion, yeast




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