Crystal structure of a lipid G protein-coupled receptor

Michael A. Hanson, Christopher B. Roth, Euijung Jo, Mark T. Griffith, Fiona L. Scott, Greg Reinhart, Hans Desale, Bryan Clemons, Stuart M. Cahalan, Stephan C. Schuerer, M. Germana Sanna, Gye Won Han, Peter Kuhn, Hugh Rosen, Raymond C. Stevens

Research output: Contribution to journalArticlepeer-review

522 Scopus citations


The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P 1-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P 1, resulting in the modulation of immune and stromal cell responses.

Original languageEnglish (US)
Pages (from-to)851-855
Number of pages5
Issue number6070
StatePublished - Feb 17 2012
Externally publishedYes

ASJC Scopus subject areas

  • General


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