A Lipid Sensing GPCR

Sci. Signal.  21 Feb 2012:
Vol. 5, Issue 212, pp. ec59
DOI: 10.1126/scisignal.2002967

Sphingosine 1-phosphate (S1P) is a sphingolipid that binds to the G protein–coupled receptor S1P receptor subtype 1 (S1PR1) to activate signaling pathways involved in regulation of the vascular and immune systems. Hanson et al. determined the crystal structure of S1PR in complex with an antagonist sphingolipid mimic. Ligand access to the receptor from the extracellular milieu is occluded, and a gap between helices I and VII may provide ligand access from within the membrane. The structural information, together with mutagenesis and structure activity relationship data, provides insight into the molecular recognition events that modulate signaling.

M. A. Hanson, C. B. Roth, E. Jo, M. T. Griffith, F. L. Scott, G. Reinhart, H. Desale, B. Clemons, S. M. Cahalan, S. C. Schuerer, M. G. Sanna, G. W. Han, P. Kuhn, H. Rosen, R. C. Stevens, Crystal structure of a lipid G protein–coupled receptor. Science 335, 851–855 (2012). [Abstract] [Full Text]