Targeting the protein folding transition state by mutation: Large scale (un)folding rate accelerations without altering native stability.

ABSTRACT: Proteins are constantly undergoing folding and unfolding transitions, with rates that determine their homeostasis in vivo and modulate their biological function. The ability to optimize these rates without affecting overall native stability is hence highly desirable for protein engineering and design. The great challenge is, however, that mutations generally affect folding and unfolding rates with inversely complementary fractions of the net free energy change they inflict on the native state. Here we address this challenge by targeting the folding transition state (FTS) of chymotrypsin inhibitor 2 (CI2), a very slow and stable two-state folding protein with an FTS known to be refractory to change by mutation. We first discovered that the CI2's FTS is energetically taxed by the desolvation

SUBMITTER: Campos LA 

PROVIDER: S-EPMC11168068 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature