Роль липидного окружения в формировании димера гликофорина А
Transmembrane α-helical domains are common structural elements in membrane proteins structure. They are involved into functioning of receptors and ion channels. Protein-protein interactions in lipid environment underlie the function of the most membrane systems. The properties of lipid environment can modulate the activity of membrane proteins, such as receptor tyrosine kinases. Glycophorin A is a glycoprotein that forms a very stable dimer. Its transmembrane domain is known as a good model system to study dimerization of α-helices. The major mechanism of the disturbance of a dimer by point mutations is thought to be a change of protein-protein contacts, but the role of the membrane is not well understood. In present work we study the behavior of transmembrane segment of human glycophorin A and two mutant forms G83A and T87V using molecular dynamics simulations in lipid environment. The free energy of dimerization has been estimated and the analysis of lipid properties was done. We propose different mechanisms for each mutation: T87V strongly changes protein-protein contacts. For G83A we demonstrate with the decomposition approach the major contribution of non-favorable protein-lipid contacts coupled with the redistribution interfacial protein-protein interactions. For monomers and dimers of all three forms of glycophorin A we found lipid binding sites near the interface of dimerization in the hydrophobic region of the bilayer. Surprisingly, in the case of monomers lipid acyl chains bind to the interfacial residues. Thus, the membrane plays an active role in dimer formation.