Publication: Interaction of myelin basic protein with membranes: a molecular dynamics simulation with a mixed negatively-charged DMPC-DMPS bilayer
All || By Area || By Year| Title | Interaction of myelin basic protein with membranes: a molecular dynamics simulation with a mixed negatively-charged DMPC-DMPS bilayer | Authors/Editors* | E. Polverini, M. De Donatis, G. Harauz |
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| Where published* | ECCB 2012 - European Conference on Computational Biology |
| How published* | Proceedings |
| Year* | 2012 |
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| Abstract |
Myelin basic protein (MBP) is a highly basic multifunctional protein of the central nervous system, whose principal role is to maintain the compactness and integrity of the myelin sheath, acting as a âbiological glueâ. Because of its involvement in human demyelinating diseases, the investigation of the interaction of MBP with membrane is particularly relevant. The three-dimensional structure of MBP is still unknown; three regions of the protein can potentially be amphipathic alpha-helices and, therefore, are good candidates as interaction sites with membranes. In this study, we investigate the N-terminal segment, ranging from residue Arg29 to Gly48, which also contains a double Phe-Phe site that can strongly contribute to anchor this region to the membrane. Molecular dynamics simulations were performed on this peptide in the presence of both neutral (DMPC) and mixed neutral-negatively charged (DMPC-DMPS) bilayers. The results show a deeper penetration of the amphipathic helix into the DMPC membrane, anchored by its hydrophobic surface. In the mixed DMPC-DMPS bilayer, instead, the peptide remains more at the bilayer surface, due to the stronger electrostatic interaction of MBP basic residues with the negative charges of the headgroups. In both cases, the helix conformation is very stable. Several post-translational modifications (PTMs) are known to be present all along the whole protein, acting as a âmolecular barcodeâ that modulates the interaction of MBP with membrane or with signaling proteins. The effect of Arg31 deimination and Thr33 and Ser44 phosphorylation are currently under investigation both in the neutral and in the mixed bilayer system. |
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