Effects of palmitoylation on membrane protein partitioning into lipid domains in model cellular membranes

Abstract The partitioning of membrane proteins into lipid domains in cellular membranes is closely associated with the realization of the protein functions and it is influenced by various factors such as the post-translational modification of palmitoylation. However, the molecular mechanism of the effect of palmitoylation on membrane protein partitioning into the lipid domains remains elusive. In this work, taking human peripheral myelin protein 22 (PMP22) as an example, we employ coarse-grained molecular dynamics simulations to investigate the partitioning of both the natural PMP22 and the palmitoylated PMP22 (pal-PMP22) into the lipid domains of model myelin membranes. The results indicate that palmitoylation drives PMP22 to localize at the boundary of the liquid-ordered (Lo) and liquid-disordered (Ld) domains and increases the possibility of PMP22 partitioning into the Lo domains by changing the hydrophobic length of the proteins and perturbing the ordered packing of tails of the saturated lipids in the Lo domains. This work offers some novel insights into the role of palmitoylation in modulating the function of membrane proteins in cellular membranes.