The role of lipid environment in dimerization of protein helical transmembrane domains
Transmembrane domains of the most membrane proteins consist of single α-helices or their bundles. They take part in the functioning of receptors and ion channels and provide spatial structure formation. Thus, helix-helix interactions in lipid environment are involved in crucial processes of cell functioning. The concept of dimerization motifs representing protein-protein interactions as direct residue contacts is now replaced with the model of active membrane medium affecting embedded proteins. In the present work computer molecular dynamics simulations have been used to study the behavior of the transmembrane segment of glycophorin A and two artificial polypeptides (based on polyalanine and polyleucine) in hydrated lipid bilayers. It was demonstrated that both monomers and dimers present lipid interaction sites on the surface of helical transmembrane segments. In the case of glycophorin A monomer, the most prominent interaction site corresponds to the dimerization interface. The redistribution of bound lipid molecules during dimer formation stabilizes the dimeric state with the entropy contribution into the association free energy.