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Lipid environment promotes dimerization of transmembrane helices
Membrane receptors are among the most important molecules in the cell. Their functioning determines the response of the cell to the external conditions. Also, they provide cellular communication and recognitionmechanisms. So, their proper functioning is a vital question of life. There is a lot of data today about these receptors. Many three-dimensional (3D) structures are known, genetic causes of some diseases are determined andmany therapeutic agents acting on the membrane proteins are developed. But today with all this knowledge we cannot exactly predict the effects of new mutations in these proteins on their activity and cannot decipher the mechanisms of their action in detail. On the other side, cell membrane consists of phospholipids acting as a matrix for the proteins and other molecules like glycolipids. Of course, exact lipid composition of the membrane affects the proteins behavior, but this phenomenon is reversible. Many papers describe how single-point mutations act on the protein activity, another large area of study includes determination of the influence from the lipid bilayer properties. But little is said about how the protein itself induces local perturbations on the membrane. Taking this into account, we decided to examine the simplest case of the membrane protein with a help of atomistic computer simulations of molecular dynamics. Using transmembrane (TM) helical peptide representing TMdomain of human glycophorinA in hydrated lipid bilayer, we showed that it can induce local perturbations of lipid properties, and the characteristic size of the pattern is 10-15 ÅA. So, the peptides can feel each other on large distances (about 20 Å), and this estimation is confirmed by calculation of the association free energy. We determined that the interaction interface for dimer formation also serves as a binding site for lipids. They are removed from this site during dimerization process, but stay nearby in the dimer structure filling the gaps next to the contact of helices. We assume that native sequences generate specific distributions of lipids around them to find each other in the membrane and have specific surface relief to strengthen the interaction in case of dimerizing proteins by lipid binding to the formed dimer. © 2015 by Nova Science Publishers, Inc. All rights reserved.
