The migration of cells around the body is an important factor in cancer development and the establishment of infection. Movement is induced by small proteins called chemokines, so for a specific function, migration is controlled by a relevant chemokine binding to its respective receptor. Chemokines bind to members of a family of receptors known as G protein–coupled receptors, which span cell membranes to mediate between external signals from chemokines and internal mechanisms. The chemokine receptor CXCR4 is implicated in many types of cancer and in infection, and Wu et al. (see the Report by Chien et al.) report on a series of crystal structures obtained for CXCR4 bound to small molecules. In every case, the same homodimer structure was observed, suggesting that the interface is functionally relevant. These structures offer insights into the interactions between CXCR4 and its natural chemokine, as well as with the virus HIV-1.
B. Wu, E. Y. T. Chien, C. D. Mol, G. Fenalti, W. Liu, V. Katritch, R. Abagyan, A. Brooun, P. Wells, F. C. Bi, D. J. Hamel, P. Kuhn, T. M. Handel, V. Cherezov, R. C. Stevens, Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330, 1066–1071 (2010). [Abstract] [Full Text]
E. Y. T. Chien, W. Liu, Q. Zhao, V. Katritch, G. W. Han, M. A. Hanson, L. Shi, A. H. Newman, J. A. Javitch, V. Cherezov, R. C. Stevens, Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330, 1091–1095 (2010). [Abstract] [Full Text]