Structural insights into neutrophilic migration revealed by the crystal structure of the chemokine receptor CXCR2 in complex with the first PDZ domain of NHERF1.

ABSTRACT: Neutrophil plays an essential role in host defense against infection, but uncontrolled neutrophilic infiltration can cause inflammation and severe epithelial damage. We recently showed that CXCR2 formed a signaling complex with NHERF1 and PLC-2, and that the formation of this complex was required for intracellular calcium mobilization and neutrophilic transepithelial migration. To uncover the structural basis of the complex formation, we report here the crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal sequence of CXCR2 at 1.16 Å resolution. The structure reveals that the CXCR2 peptide binds to PDZ1 in an extended conformation with the last four residues making specific side chain interactions. Remarkably, comparison of the structure to previously studied PDZ1 doma

SUBMITTER: Lu G 

PROVIDER: S-EPMC3788737 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature