T-Cell Receptor Variable β Domains Rigidify During Affinity Maturation.

ABSTRACT: We investigated T-cell receptor variable β chains binding to the superantigen staphylococcal enterotoxin C3 (SEC 3) with structure information in different stages of affinity maturation. Metadynamics in combination with molecular dynamics simulations allow to access the micro-to-millisecond timescale and reveal a strong effect of energetically significant mutations on the flexibility of the antigen-binding site. The observed changes in dynamics of the complementarity determining region (CDR) loops, especially the CDR 2, and HV 4 loop on this specific pathway of affinity maturation are reflected in their structural diversity, thermodynamics of conformations and kinetics of structural transitions. In addition, this affinity maturation pathway follows the concept of conformational selection,

SUBMITTER: Fernandez-Quintero ML 

PROVIDER: S-EPMC7066139 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature