Rules of engagement: Determinants of chemokine receptor activation and selectivity by CCL27 and CCL28.

ABSTRACT: The distinct functional roles of chemokines CCL27 and CCL28 in epithelial immunity of skin and mucosal tissues, respectively, are coordinated by their shared receptor, CCR10, and the CCL28-specific receptor, CCR3. To identify determinants of receptor activation, internalization and binding specificity, we conducted structure-function studies focused on the N termini of these two chemokines. Deletion of two N-terminal residues of CCL27 resulted in a CCR10 antagonist, highlighting the critical roles of these residues in driving receptor pharmacology. Extension with a Phe produced a CCR10 superagonist by occupying a unique subpocket in the receptor. Swapping the CCL28 N terminus onto the CCL27 globular domain (NT28-CCL27) also resulted in a superagonist of CCR10, but the opposite swap (NT27-C

SUBMITTER: Huang M 

PROVIDER: S-EPMC12556802 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature