Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics.

ABSTRACT: The evolution of proteins with novel function is thought to start from precursor proteins that are conformationally heterogeneous. The corresponding genes may be duplicated and then mutated to select and optimize a specific conformation. However, testing this idea has been difficult because of the challenge of quantifying protein flexibility and conformational heterogeneity as a function of evolution. Here, we report the characterization of protein heterogeneity and dynamics as a function of evolution for the antifluorescein antibody 4-4-20. Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular dynamics simulations, we demonstrate that evolution localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing muta

SUBMITTER: Zimmermann J 

PROVIDER: S-EPMC1564241 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature