The chemokine X-factor: Structure-function analysis of the CXC motif at CXCR4 and ACKR3.

ABSTRACT: The human chemokine family consists of 46 protein ligands that induce chemotactic cell migration by activating a family of 23 G protein-coupled receptors. The two major chemokine subfamilies, CC and CXC, bind distinct receptor subsets. A sequence motif defining these families, the X position in the CXC motif, is not predicted to make significant contacts with the receptor, but instead links structural elements associated with binding and activation. Here, we use comparative analysis of chemokine NMR structures, structural modeling, and molecular dynamic simulations that suggested the X position reorients the chemokine N terminus. Using CXCL12 as a model CXC chemokine, deletion of the X residue (Pro-10) had little to no impact on the folded chemokine structure but diminished CXCR4 agonist a

SUBMITTER: Wedemeyer MJ 

PROVIDER: S-EPMC7535910 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature