Correlation of fitness landscapes from three orthologous TIM barrels originates from sequence and structure constraints.

ABSTRACT: Sequence divergence of orthologous proteins enables adaptation to environmental stresses and promotes evolution of novel functions. Limits on evolution imposed by constraints on sequence and structure were explored using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Analysis of beneficial mutations pointed to an unexpected, long-range allosteric pathway towards the active site of the protein. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel f

SUBMITTER: Chan YH 

PROVIDER: S-EPMC5343507 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature