Activation mechanisms of the first sphingosine-1-phosphate receptor.

ABSTRACT: Activation of the first sphingosine-1-phosphate receptor (S1PR₁ ) promotes permeability of the blood brain barrier, astrocyte and neuronal protection, and lymphocyte egress from secondary lymphoid tissues. Although an agonist often activates the S1PR₁ , the receptor exhibits high levels of basal activity. In this study, we performed long-timescale molecular dynamics and accelerated molecular dynamics (aMD) simulations to investigate activation mechanisms of the ligand-free (apo) S1PR₁ . In the aMD enhanced sampling simulations, we observed four independent events of activation, which is characterized by close interaction between Y311^7.53 and Y221^5.58 and increased distance between the intracellular ends of transmembrane (TM) helices 3

SUBMITTER: Caliman AD 

PROVIDER: S-EPMC5441409 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature