NR AUOV
AU Tutar,Y.; Song,Y.; Masison,D.C.
TI Primate chaperones Hsc70 (constitutive) and Hsp70 (induced) differ functionally in supporting growth and prion propagation in Saccharomyces cerevisiae
QU Genetics 2006 Feb; 172(2): 851-61
PT journal article
AB Hsp70's 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 cochaperones. Eukaryotes have constitutive (Hsc70) and stress-inducible (iHsp70) isoforms, but their functions have not been systematically compared. Using a yeast system to evaluate heterologous Hsp70's we find that 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 that (i) the Hsc70-iHsp70 distinction resided in the ATPase domain, (ii) substrate-binding domains of Hsp70's 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 cochaperones.
MH Adenosinetriphosphatase/physiology; Animals; Arabidopsis/genetics; Blotting, Western; Cell Proliferation; Comparative Study; HSC70 Heat-Shock Proteins/*biosynthesis/genetics/*physiology; Heat; Heat-Shock Proteins/metabolism; Prions/*biosynthesis; Protein Denaturation; Protein Folding; Protein Isoforms/biosynthesis/genetics/physiology; Protein Structure, Tertiary; Research Support, N.I.H., Intramural; Saccharomyces cerevisiae/genetics/growth & development/*physiology; Saccharomyces cerevisiae Proteins/metabolism; Saguinus/*genetics
AD Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0851, USA
SP englisch
PO USA