Phosphatidylserine-Induced Conformational Modulation of Immune Cell Exhaustion-Associated Receptor TIM3.

ABSTRACT: In the face of chronic cancers and protracted viral infections, human immune cells are known to adopt an exhausted state in which their effector functions are lost. In recent years, a number of inhibitory receptors have been connected to the immune cell exhaustion phenotype; furthermore, ligands capable of activating these receptors have been discovered. The molecular mechanisms by which these ligands affect the exhausted states of immune cells, however, are largely unknown. Here, we present the results of molecular dynamics simulations of one potential exhaustion-associated system: the complex of human inhibitory receptor TIM3 (hTIM3) and its ligand phosphatidylserine (PSF). We find that PSF fundamentally alters the electrostatic environment within hTIM3's Ca²⁺ binding site, fa

SUBMITTER: Weber JK 

PROVIDER: S-EPMC5648779 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature