Peripheral positions encode transport specificity in the small multidrug resistance exporters.

ABSTRACT: In secondary active transporters, a relatively limited set of protein folds have evolved diverse solute transport functions. Because of the conformational changes inherent to transport, altering substrate specificity typically involves remodeling the entire structural landscape, limiting our understanding of how novel substrate specificities evolve. In the current work, we examine a structurally minimalist family of model transport proteins, the small multidrug resistance (SMR) transporters, to understand the molecular basis for the emergence of a novel substrate specificity. We engineer a selective SMR protein to promiscuously export quaternary ammonium antiseptics, similar to the activity of a clade of multidrug exporters in this family. Using combinatorial mutagenesis and deep sequencin

SUBMITTER: Burata OE 

PROVIDER: S-EPMC11194549 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature