기계공학부 구성원들의 많은 관심과 참여 부탁 드립니다.

▣ 주   제: Mechanics and Dynamics of Immune Receptors

▣ 연   사: 황원묵 교수

▣ 소   속: Department of Biological Engineering, Texas A&M University

▣ 일   시: 2022. 6. 30.(Thu) 10:00

▣ 장   소: 제4공학관 D404호 

▣ 초   청: 이형석 교수

▣ 초   록

The αβT-cell receptor (TCRαβ) recognizes 8-10~aa antigenic peptide loaded on the major histocompatibility complex (pMHC) molecule with exquisite sensitivity, with a signal-to-noise ratio of 1 in 105. Yet, the equilibrium binding affinity of cognate and non-cognate pMHCs are similar and weak, on the order of micromolar range. Recent experimental findings suggest that application of physiological-level picoNewton forces to the TCRαβ-pMHC complex increases the bond

lifetime in ligand-dependent manner. This suggests that TCRαβ-pMHC system exhibits catch bond behavior that mechanically enhances antigen discrimination. We address the atomistic mechanism for the activation of the catch bond by performing all-atom molecular dynamics simulation of TCRαβ-pMHC complexes under picoNewton forces and their variants. By comparing subdomain motion and dynamics of interfacial contacts, we find that the applied load suppresses certain modes of domain

motion that have destabilizing effect on the TCRαβ-pMHC interface in the absence of load. The dynamical activation of catch bond also allows for allosteric control of the interface by altering the motion of distal domains. The dynamical mechanism also has implications in other types of T-cell receptors.