Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate

Authors

Abby L. Parrill, University of Memphis
De An Wang, University of Tennessee Health Science CenterFollow
Debra L. Bautista, University of MemphisFollow
James R. Van Brocklyn, The Ohio State University
Zsolt Lorincz, University of Tennessee Health Science Center
David J. Fischer, University of Tennessee Health Science CenterFollow
Daniel L. Baker, University of Tennessee Health Science CenterFollow
Karoly Liliom, University of Tennessee Health Science CenterFollow

Abstract

Originating from its DNA sequence, a computational model of the Edg1 receptor has been developed that predicts critical interactions with its ligand, sphingosine 1-phosphate. The basic amino acids Arg120 and Arg292 ion pair with the phosphate, whereas the acidic Glu121 residue ion pairs with the ammonium moiety of sphingosine 1-phosphate. The requirement of these interactions for specific ligand recognition has been confirmed through examination of site-directed mutants by radioligand binding, ligand-induced [35S]GTPγS binding, and receptor internalization assays. These ion-pairing interactions explain the ligand specificity of the Edg1 receptor and provide insight into ligand specificity differences within the Edg receptor family. This computational map of the ligand binding pocket provides information necessary for understanding the molecular pharmacology of this receptor, thus underlining the potential of the computational method in predicting ligand-receptor interactions.

Publication Title

Journal of Biological Chemistry

Recommended Citation

Parrill, A., Wang, D., Bautista, D., Van Brocklyn, J., Lorincz, Z., Fischer, D., Baker, D., & Liliom, K. (2000). Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate. Journal of Biological Chemistry, 275 (50), 39379-39384. https://doi.org/10.1074/jbc.M007680200