signal transduction; cholesterol; membrane protein; X-ray crystallography; cryo-electron microscopy; electron paramagnetic resonance
Cannac Fabien, Qi Chao, Falschlunger Julia, Hausmann George, Basler Konrad, Korkhov Volodymyr M. (2020), Cryo-EM structure of the Hedgehog release protein Dispatched, in Science Advances
, 6(16), eaay7928-eaay7928.
Graeber Elisabeth, Korkhov Volodymyr M. (2020), Expression, Purification, and Structural Biology of Membrane Proteins
, Springer US, New York, NY.
Graeber Elisabeth, Korkhov Volodymyr M. (2019), Characterisation of the ligand binding sites in the translocator protein TSPO using the chimeric bacterial-mammalian constructs, in Protein Expression and Purification
, 164, 105456-105456.
Qi Chao, Di Minin Giulio, Vercellino Irene, Wutz Anton, Korkhov Volodymyr M. (2019), Structural basis of sterol recognition by human hedgehog receptor PTCH1, in Science Advances
, 5(9), eaaw6490-eaaw6490.
Qi Chao, Sorrentino Simona, Medalia Ohad, Korkhov Volodymyr M. (2019), The structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein, in Science
, 364(6438), 389-394.
Graeber Elisabeth, Korkhov Volodymyr M. (2018), Expression and purification of the mammalian translocator protein for structural studies, in PLOS ONE
, 13(6), e0198832-e0198832.
Vercellino Irene, Rezabkova Lenka, Olieric Vincent, Polyhach Yevhen, Weinert Tobias, Kammerer Richard A., Jeschke Gunnar, Korkhov Volodymyr M. (2017), Role of the nucleotidyl cyclase helical domain in catalytically active dimer formation, in Proceedings of the National Academy of Sciences
, 114(46), E9821-E9828.
Membrane proteins are at the core of multiple cellular processes. This research project is aimed at elucidation of two important functions of membrane proteins: (i) signal transduction, and (ii) cholesterol recognition. Among the key tasks performed by membrane proteins is signal transduction, whereby extracellular signals received by the cell surface receptors are conveyed across the membrane to effector proteins. The effectors, some of which are integral membrane proteins, play a crucial role in cellular signalling. They convert the sensory input from outside the cell into a biochemical response inside the cell, leading to profound changes in cellular physiology. However, despite the importance of membrane-integral effector proteins in physiology, little is known about their structure, mechanism and modes of regulation by other signaling molecules. In addition to signal transduction, various membrane proteins are also involved in the recognition and translocation of a number of substrates, including ions, small molecule solutes and lipids, across the biological membranes. One such substrate is cholesterol, an essential component of many eukaryotic cell membranes. Many biological functions of cholesterol are determined by its interactions with membrane proteins, yet the current understanding of the molecular details of such interactions is insufficient. Using a combination of biochemical, biophysical and structural analysis, including EPR, cryo-EM and X-ray crystallography, I shall work towards unraveling the molecular details of structure and molecular mechanisms of membrane proteins involved in signal transduction and cholesterol recognition. The results will provide insights into these exciting branches of molecular biology, and will be of broad significance for biomedical research.