Effects of Lid Domain Structural Changes on the Interactions between Peripheral Myelin Protein 2 and a Lipid Bilayer

Peripheral myelin protein 2 (P2) plays an important role in the stacking of the myelin membrane and lipid transport. Here we investigate the interactions between P2 and a model myelin membrane using molecular dynamics simulations, focusing on the effect of the L27D mutation and conformational changes in the alpha 2-helix in the lid domain of P2. The L27D mutation weakens the binding of the lid domain of P2 on the membrane. The alpha 2-helix is either folded or unfolded on the membrane. Compared with the alpha 2-helix structure in water, the membrane stabilizes the structure of the alpha 2-helix, whereas the unfolding of the alpha 2-helix reduces the binding affinity of P2 on the membrane. These findings reveal the energetics of the mutant and the structural changes of P2 on the interactions between the protein and the lipid bilayer and help us to understand the microscopic mechanism of the formation of the myelin sheath structure and some neurological disorders.