Cell Biology

Small Changes Have Big Consequences

See allHide authors and affiliations

Science  26 Aug 2011:
Vol. 333, Issue 6046, pp. 1073
DOI: 10.1126/science.333.6046.1073-a

Protein folding and the maintenance of a healthy proteome often involve molecular chaperones of the heat shock protein 70 (Hsp70) family. The basis of functional distinctions of highly homologous and functionally redundant Hsp70s is unknown. Nearly identical yeast cytosolic Hsp70s, Ssa1p and Ssa2p, function differently in the propagation of yeast prions and in a vacuole-import and protein-degradation pathway involved in regulating levels of gluconeogenesis enzymes. By swapping amino acids, Sharma and Masison show that a single amino acid difference in the nucleotide-binding regulatory domain of the Ssa proteins is the basis for the functional distinction in both processes. It seems that this small structural difference affects regulation of Hsp70 by cofactors rather than by altering intrinsic Hsp70 activity. Thus, subtle changes in Hsp70 structure may have evolved to confer functional specificity without affecting overall Hsp70 function.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1107421108 (2011).

Navigate This Article