Publication: Molecular dynamics simulations in the presence of lipids on a

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Title Molecular dynamics simulations in the presence of lipids on a
Authors/Editors* E. Polverini, G. Harauz
Where published* XIII European Conference on the Spectroscopy of Biological Molecules, Palermo, Italy
How published* Proceedings
Year* 2009
Myelin basic protein (MBP) is a multifunctional protein of the central nervous system whose principal role is to maintain the compactness and integrity of the myelin sheath, the multilamellar membrane wrapped around nerve axons that allows efficient transmission of action potentials along them. MBP is involved in human demyelinating diseases and it is a candidate autoantigen in multiple sclerosis. However, MBP also interacts with other proteins such as cytoskeletal and signaling proteins, adapting its structure to its different roles. The three-dimensional structure of MBP is still unknown, due to its intrinsic flexibility and the dependence of conformation on local environment. This study investigates the conformation and dynamics of a highly conserved central fragment of MBP, consisting of two consecutive regions with different relevant functionalities. The first one is associated with the membrane and comprises the primary immunodominant epitope in multiple sclerosis; the second one was predicted to be a ligand for SH3-domains of signaling proteins. Molecular dynamics simulations were performed both in aqueous environment only and in the presence of a dodecylphosphocholine micelle, starting from a structure extrapolated from experimental data [1]. The results confirm the experimental hypothesis and provide further information at atomic detail. In water, a flexible starting structure forms a small transient alpha-helix in the first region, and a core of poly-proline type II (PPII) helix in the second one. In the micelle system, the first region remains anchored to the lipids in an alpha-helical conformation, while the proline-rich second region is a long PPII helix pointing outwards, ready to interact with signaling proteins.

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