Chemokine receptor oligomerization: functional considerations

The chemokines, a family of structurally related chemoattractant proteins that bind to specific seven-transmembrane receptors linked to G proteins, trigger a broad array of biological responses ranging from cell polarization, movement, immune and inflammatory responses to prevention of HIV-1 infection. Chemokine-mediated cell activation was thought to be due to the binding of a monomeric chemokine to its monomeric receptor. Chemokine biology is nonetheless more complex than was initially predicted, as several studies suggest that chemokines can dimerize and that their receptors are found as dimers and/or higher order oligomers at the cell surface. There is also evidence that they cluster in arrays, rather like bundles of cigars. Here we evaluate how these arrays might be organized, the influence of ligand levels and receptor expression on them, and their influence on chemokine function.