Interactions between the cell and its environment, as well as between cellular compartments, occur at the biological membranes. Extracellular signals are sensed by the receptors embedded in the plasma membrane. Following multiple protein-protein interactions within and near the membrane surface, these signals are transmitted across the membrane, resulting in profound changes in cellular physiology. The process of signal transduction is of paramount importance in physiological and pathophysiological processes involving communication between cells. Despite the tremendous progress in understanding the molecular mechanisms of receptors (such as GPCRs), the steps that follow the initial chemo- or photoreception, i.e. downstream signal transduction events, are not well understood.
Membrane proteins are also involved in the recognition and transport of a variety of substrates, including ions, small molecule solutes and lipids across the membrane. One such substrate is cholesterol - an integral part of many biological membranes, and a key regulatory factor not only for proteins involved in cellular signaling, but for membrane proteins in general. Various types of interactions between cholesterol and membrane proteins have been described to date, including binding, transport and enzymatic modifications. Many of these processes are directly associated with human pathologies, which warrants detailed investigation of the common principles underlying membrane protein-cholesterol interactions.
The Korkhov group focuses on these two exciting topics of membrane protein biology: (i) molecular mechanisms of signal transduction, and (ii) cholesterol recognition by membrane proteins. Using a multidisciplinary approach including methods of membrane protein biochemistry, biophysics and structural biology, we aim to understand the structure-function relationships of physiologically and medically important membrane-integral proteins and protein complexes involved in these processes.