Dynamic modeling of EDG1 receptor structural changes induced by site-directed mutations
Abstract
EDG1 is a member of the G protein coupled receptor family and serves as a cellular receptor responsive to phospholipids. EDG1 binds sphingosine-1-phosphate (SPP) with high affinity and lysophophatidic acid (LPA) with low affinity. A model has been developed, based on an experimentally based model of the structure of rhodopsin, to evaluate the features that contribute to the different binding affinities of phospholipids for EDG1. The residues predicted by the model to be important in binding have previously been reported. Twenty mutations expressed transiently in HEK293 cells were evaluated by radioligand binding assays and MAP-kinase assays of receptor activation. Seventeen of these mutations are well explained by the current model. The remaining three mutations and three additional control mutations have been modeled using molecular dynamics. Changes in the exposed surface areas of amino acids in the binding pocket reflect the changes in SPP binding observed for the modeled mutations. (C) 2000 Elsevier Science B.V.
Publication Title
Journal of Molecular Structure: THEOCHEM
Recommended Citation
Bautista, D., Baker, D., Wang, D., Fischer, D., Van Brocklyn, J., Spiegel, S., Tigyi, G., & Parrill, A. (2000). Dynamic modeling of EDG1 receptor structural changes induced by site-directed mutations. Journal of Molecular Structure: THEOCHEM, 529 (2022-01-03), 219-224. https://doi.org/10.1016/S0166-1280(00)00549-2
