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 journalArticle

445 Citations (Scopus)

Abstract

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
Pages (from-to)851-855
Number of pages5
JournalScience
Volume335
Issue number6070
DOIs
StatePublished - Feb 17 2012
Externally publishedYes

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Protein
Lipids
Crystal
Phosphate
Cells
Heart Rate
Integrity
Ralph Waldo Emerson
Modulation
Antagonist
Modeling

ASJC Scopus subject areas

  • General
  • History and Philosophy of Science

Cite this

Hanson, M. A., Roth, C. B., Jo, E., Griffith, M. T., Scott, F. L., Reinhart, G., ... Stevens, R. C. (2012). Crystal structure of a lipid G protein-coupled receptor. Science, 335(6070), 851-855. https://doi.org/10.1126/science.1215904

Crystal structure of a lipid G protein-coupled receptor. / Hanson, Michael A.; Roth, Christopher B.; Jo, Euijung; Griffith, Mark T.; Scott, Fiona L.; Reinhart, Greg; Desale, Hans; Clemons, Bryan; Cahalan, Stuart M.; Schuerer, Stephan C; Sanna, M. Germana; Han, Gye Won; Kuhn, Peter; Rosen, Hugh; Stevens, Raymond C.

In: Science, Vol. 335, No. 6070, 17.02.2012, p. 851-855.

Research output: Contribution to journalArticle

Hanson, MA, Roth, CB, Jo, E, Griffith, MT, Scott, FL, Reinhart, G, Desale, H, Clemons, B, Cahalan, SM, Schuerer, SC, Sanna, MG, Han, GW, Kuhn, P, Rosen, H & Stevens, RC 2012, 'Crystal structure of a lipid G protein-coupled receptor', Science, vol. 335, no. 6070, pp. 851-855. https://doi.org/10.1126/science.1215904
Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G et al. Crystal structure of a lipid G protein-coupled receptor. Science. 2012 Feb 17;335(6070):851-855. https://doi.org/10.1126/science.1215904
Hanson, Michael A. ; Roth, Christopher B. ; Jo, Euijung ; Griffith, Mark T. ; Scott, Fiona L. ; Reinhart, Greg ; Desale, Hans ; Clemons, Bryan ; Cahalan, Stuart M. ; Schuerer, Stephan C ; Sanna, M. Germana ; Han, Gye Won ; Kuhn, Peter ; Rosen, Hugh ; Stevens, Raymond C. / Crystal structure of a lipid G protein-coupled receptor. In: Science. 2012 ; Vol. 335, No. 6070. pp. 851-855.
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