Binding Characteristics of Sphingosine-1-Phosphate to ApoM hints to Assisted Release Mechanism via the ApoM Calyx-Opening.

ABSTRACT: Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator carried by the HDL-associated apoM protein in blood, regulating many physiological processes by activating the G protein-coupled S1P receptor in mammals. Despite the solved crystal structure of the apoM-S1P complex, the mechanism of S1P release from apoM as a part of the S1P pathway is unknown. Here, the dynamics of the wild type apoM-S1P complex as well as of mutants were investigated by means of atomistic molecular dynamics simulations. The potential of mean force for S1P unbinding from apoM reflected a large binding strength of more than 60 kJ/mol. This high unbinding free energy for S1P underlines the observed specificity of the physiological effects of S1P as it suggests that the spontaneous release of S1P from apoM is unlik

SUBMITTER: Zhang H 

PROVIDER: S-EPMC4967915 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature