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Sci. Signal., 22 May 2012
Vol. 5, Issue 225, p. pe23
[DOI: 10.1126/scisignal.2003160]


Structure of the First Sphingosine 1-Phosphate Receptor

Abby L. Parrill1*, Santiago Lima2, and Sarah Spiegel2*

1 Department of Chemistry, The University of Memphis, 213 Smith Chemistry Building, Memphis, TN 38152, USA.
2 Department of Biochemistry and Molecular Biology, Virginia Commonwealth University (VCU) School of Medicine, 1101 East Marshall Street, Richmond, VA 23298, USA.

Abstract: The sphingosine 1-phosphate receptor 1 (S1P1) and its ligand, sphingosine 1-phosphate (S1P), have now emerged as critical regulators of lymphocyte trafficking, vascular development and integrity, and immunity. S1P1 is targeted by the phosphorylation product of fingolimod, which has been approved for the treatment of multiple sclerosis. The recent progress in the structural biology of heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors has now enabled the elucidation of the structure of S1P1. Analysis of the structure, along with structure activity and mutagenesis analysis, highlighted key interactions associated with the binding of S1P and agonists and suggested that the ligand may gain access to the binding pocket by lateral diffusion within the plasma membrane. The S1P1 crystal structure will be helpful for designing ligands that specifically target S1P1.

* Corresponding authors. E-mail: aparrill{at} (A.L.P.); sspiegel{at} (S.S.)

Citation: A. L. Parrill, S. Lima, S. Spiegel, Structure of the First Sphingosine 1-Phosphate Receptor. Sci. Signal. 5, pe23 (2012).

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