Rheostat functional outcomes occur when substitutions are introduced at nonconserved positions that diverge with speciation.

ABSTRACT: When amino acids vary during evolution, the outcome can be functionally neutral or biologically-important. We previously found that substituting a subset of nonconserved positions, "rheostat" positions, can have surprising effects on protein function. Since changes at rheostat positions can facilitate functional evolution or cause disease, more examples are needed to understand their unique biophysical characteristics. Here, we explored whether "phylogenetic" patterns of change in multiple sequence alignments (such as positions with subfamily specific conservation) predict the locations of functional rheostat positions. To that end, we experimentally tested eight phylogenetic positions in human liver pyruvate kinase (hLPYK), using 10-15 substitutions per position and biochemical assays tha

SUBMITTER: Swint-Kruse L 

PROVIDER: S-EPMC8376419 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature