Latent effects of Hsp90 mutants revealed at reduced expression levels.

ABSTRACT: In natural systems, selection acts on both protein sequence and expression level, but it is unclear how selection integrates over these two dimensions. We recently developed the EMPIRIC approach to systematically determine the fitness effects of all possible point mutants for important regions of essential genes in yeast. Here, we systematically investigated the fitness effects of point mutations in a putative substrate binding loop of yeast Hsp90 (Hsp82) over a broad range of expression strengths. Negative epistasis between reduced expression strength and amino acid substitutions was common, and the endogenous expression strength frequently obscured mutant defects. By analyzing fitness effects at varied expression strengths, we were able to uncover all mutant effects on function. The majo

SUBMITTER: Jiang L 

PROVIDER: S-EPMC3694843 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature