A MD Simulation Prediction for Regulation of N-Terminal Modification on Binding of CD47 to CD172a in a Force-Dependent Manner.

ABSTRACT: Cancer cells can evade immune surveillance through binding of its transmembrane receptor CD47 to CD172a on myeloid cells. CD47 is recognized as a promising immune checkpoint for cancer immunotherapy inhibiting macrophage phagocytosis. N-terminal post-translated modification (PTM) via glutaminyl cyclase is a landmark event in CD47 function maturation, but the molecular mechanism underlying the mechano-chemical regulation of the modification on CD47/CD172a remains unclear. Here, we performed so-called "ramp-clamp" steered molecular dynamics (SMD) simulations, and found that the N-terminal PTM enhanced interaction of CD172a with CD47 by inducing a dynamics-driven contraction of the binding pocket of the bound CD172a, an additional constraint on CYS15 on CD47 significantly improv

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC10221095 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature