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

Journal article


Publication Details

Author(s): Zhang H, Pluhackova K, Jiang Z, Böckmann R
Journal: Scientific Reports
Publisher: Nature Publishing Group: Open Access Journals - Option B
Publication year: 2016
Volume: 6
Pages range: 30655
ISSN: 2045-2322


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 unlikely. Instead, S1P release and thus the control of this bioactive lipid probably requires the tight interaction with other molecules, e.g. with the S1P receptor. Mutations of specific S1P anchoring residues of apoM decreased the energetic barrier by up to 20 kJ/mol. Moreover, the ligand-free apoM protein is shown to adopt a more open upper hydrophilic binding pocket and to result in complete closure of the lower hydrophobic cavity, suggesting a mechanism for adjusting the gate for ligand access.



FAU Authors / FAU Editors

Böckmann, Rainer Prof. Dr.
Professur für Computational Biology
Jiang, Zhenyan
Professur für Computational Biology
Pluhackova, Kristyna
Professur für Computational Biology
Zhang, Hansi
Professur für Computational Biology


How to cite

APA:
Zhang, H., Pluhackova, K., Jiang, Z., & Böckmann, R. (2016). Binding Characteristics of Sphingosine-1-Phosphate to ApoM hints to Assisted Release Mechanism via the ApoM Calyx-Opening. Scientific Reports, 6, 30655. https://dx.doi.org/10.1038/srep30655

MLA:
Zhang, Hansi, et al. "Binding Characteristics of Sphingosine-1-Phosphate to ApoM hints to Assisted Release Mechanism via the ApoM Calyx-Opening." Scientific Reports 6 (2016): 30655.

BibTeX: 

Last updated on 2019-28-02 at 06:06