Димеризация трансмембранных доменов белков: роль липидного окружения
Transmembrane (TM) helices are one of the most common structural elements in membrane proteins. Their interaction in lipid environment governs the formation of protein spatial structure formation and functioning in normal and pathology. Receptor tyrosine kinases are a wide class of protein molecules having single helix as their TM domain, so dimerization process is crucial for their functioning. But lipid environment may modulate these process, and molecular details are still unclear. In present work we use computer atomistic modeling to reveal the basis of protein-lipid interactions in a model system – human glycophorin A, its mutant forms and model polypeptides. It is shown that lipid environment makes a great contribution into free energy of TM domain association. For two known point mutations of glycophorin A we show different mechanisms of changing the dimer stability. Using long molecular dynamics simulations some protein-lipid interactions sites were detected in a hydrophobic core of the bilayer. Also we observe a correlation between lipid binding sites distribution and free energy estimations that propose entropic mechanism for lipid-induced dimerization of several TM domains. In the case of natural sequence of glycophorin A these mechanism is combined with optimal packing of protein residues.