An allosteric pathway explains beneficial fitness in yeast for long-range mutations in an essential TIM barrel enzyme.

ABSTRACT: Protein evolution proceeds by a complex response of organismal fitness to mutations that can simultaneously affect protein stability, structure, and enzymatic activity. To probe the relationship between genotype and phenotype, we chose a fundamental paradigm for protein evolution, folding, and design, the (βα)₈ TIM barrel fold. Here, we demonstrate the role of long-range allosteric interactions in the adaptation of an essential hyperthermophilic TIM barrel enzyme to mesophilic conditions in a yeast host. Beneficial fitness effects observed with single and double mutations of the canonical βα-hairpin clamps and the α-helical shell distal to the active site revealed an underlying energy network between opposite faces of the cylindrical β-barrel. We experimentally determined the fi

SUBMITTER: Chan YH 

PROVIDER: S-EPMC7454521 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature