Mutational tipping points for switching protein folds and functions.

ABSTRACT: While disordered to ordered rearrangements are relatively common, the ability of proteins to switch from one ordered fold to a completely different fold is generally regarded as rare, and few fold switches have been characterized. Here, in a designed system, we examine the mutational requirements for transitioning between folds and functions. We show that switching between monomeric 3α and 4β+α folds can occur in multiple ways with successive single amino acid changes at diverse residue positions, raising the likelihood that such transitions occur in the evolution of new folds. Even mutations on the periphery of the core can tip the balance between alternatively folded states. Ligand-binding studies illustrate that a new immunoglobulin G-binding function can be gained well before the relev

SUBMITTER: He Y 

PROVIDER: S-EPMC3278708 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature