Summary: / www.sciencexpress.org / 7 October 2010 / Page 1 / 10.1126/science.science.1194396
Chemokine receptors are critical regulators of cell
migration in the context of immune surveillance,
inflammation, and development. The G protein­coupled
chemokine receptor, CXCR4, is specifically implicated in
cancer metastasis and HIV-1 infection. Here we report
five independent crystal structures of CXCR4 bound to an
antagonist small molecule IT1t and a cyclic peptide
CVX15 at 2.5 to 3.2 angstrom resolution. All structures
reveal a consistent homodimer with an interface including
helices V and VI that may be involved in regulating
signaling. The location and shape of the ligand-binding
sites differ from other G protein­coupled receptors
(GPCRs) and are closer to the extracellular surface. These
structures provide new clues about the interactions
between CXCR4 and its natural ligand CXCL12 and with
the HIV-1 glycoprotein gp120.
Chemokine receptors are G protein­coupled receptors
(GPCRs) that, together with their small protein ligands,
regulate the migration of many different cell types, most

Source: Abagyan, Ruben - School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego

Collections: Biology and Medicine