Regulation and dynamics of yeast tryptophan permeases studied using hydrostatic pressure

Abstract

The yeast Saccharomyces cerevisiae possesses 24 amino acid permeases and their homologs, which exhibit different properties with respect to substrate specificity, capacity, and regulation. These permeases are regulated in response to physiological and nutritional changes at the transcriptional and posttranslational levels. Two permeases, Tat1 and Tat2, mediate the import of tryptophan across the plasma membrane. There is evidence showing that tryptophan uptake is the Achilles' heel of yeast physiology since a variety of adverse conditions impair its uptake, and hence limit the growth of tryptophan-auxotrophic strains. Recent studies in yeast cell biology have yielded information on the posttranslational regulatory systems of the two tryptophan permeases by ubiquitination. When cells are subjected to nutrient starvation, toxic chemicals, low temperature, or high hydrostatic pressure, Tat2 is rapidly degraded in a manner dependent on Rsp5 ubiquitin ligase. Hydrostatic pressure is a thermodynamic parameter that has recently received renewed attention in biophysics, biochemistry, and microbiology. Researchers have attempted to analyze system volume changes associated with protein unfolding, enzymatic reactions, or membrane protein functions. Here I review the literature on yeast tryptophan permeases and the properties of these permease proteins using hydrostatic pressure to investigate the dynamic structural changes of tryptophan permeases.