Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.

ABSTRACT: Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein-coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking, endothelial development, integrity, and maturation. We performed five all-atom 700 ns molecular dynamics simulations of the sphingosine 1-phosphate receptor 1 (S1P₁) based on recently released crystal structure of that receptor with an antagonist. We found that the initial movements of amino acid residues occurred in the area of highly conserved W269⁶·⁴⁸ in TM6 which is close to the ligand binding location. Those residues located in the central part of the receptor and adjacent to kinks of TM helices comprise of a transmission switch. Side chains movements of those residues w

SUBMITTER: Yuan S 

PROVIDER: S-EPMC3789783 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature