Structure-function guided modeling of chemokine-GPCR specificity for the chemokine XCL1 and its receptor XCR1.

ABSTRACT: Chemokines interact with their G protein-coupled receptors (GPCRs) through a two-step, two-site mechanism and, through this interaction, mediate various homeostatic and immune response mechanisms. Upon initial recognition of the chemokine by the receptor, the amino terminus of the chemokine inserts into the orthosteric pocket of the GPCR, causing conformational changes that trigger intracellular signaling. There is considerable structural and functional evidence to suggest that the amino acid composition and length of the chemokine amino terminus is critical for GPCR activation, complementing the size and amino acid composition of the orthosteric pocket. However, very few structures of a native chemokine-receptor complex have been solved. Here, we used a hybrid approach that combines struc

SUBMITTER: Fox JC 

PROVIDER: S-EPMC6733756 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature