The structure and function of the S1P1 receptor

Trends Pharmacol Sci. 2013 Jul;34(7):401-12. doi: 10.1016/ Epub 2013 Jun 11.


Sphingosine 1-phosphate (S1P) receptors (S1PRs) belong to the class A family of G protein-coupled receptors (GPCRs). S1PRs are widely expressed on many cell types, including those of the immune, cardiovascular, and central nervous systems. The S1PR family is rapidly gaining attention as an important mediator of many cellular processes, including cell differentiation, migration, survival, angiogenesis, calcium homeostasis, inflammation and immunity. Importantly, S1PRs are known drug targets for multiple sclerosis (MS), for which the newly developed oral therapy fingolimod, an S1PR modulator, has recently been approved for clinical use. Much progress has also recently been made in the field of structural biology and in the modeling of heterotrimeric GPCRs allowing the crystal structure of the S1PR1 subtype to be elucidated and key interactions defined. Here, we outline the structure and function of S1PR1, highlighting the key residues involved in receptor activation, signaling, transmembrane interactions, ligand binding, post-translational modification, and protein-protein interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drug Design
  • Humans
  • Ligands
  • Lysophospholipids / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Binding
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Receptors, Lysosphingolipid / chemistry
  • Receptors, Lysosphingolipid / drug effects
  • Receptors, Lysosphingolipid / metabolism*
  • Signal Transduction*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Structure-Activity Relationship


  • Ligands
  • Lysophospholipids
  • Receptors, Lysosphingolipid
  • sphingosine 1-phosphate
  • Sphingosine