Ion channels are membrane proteins that conduct ionic currents across cellular membrane and contribute to numerous physiological processes such as synaptic transmission, cell excitability and sensory transduction. Ion channels are implicated in pathogenesis of numerous human diseases and represent one of the most important drug targets. For the efficient drug design, we need detailed information about ion channel structure and function.
We study structure and function of ion channels using different biophysical and biochemical techniques including X-ray crystallography, molecular biology, substituted cysteine accessibility method and electrophysiology. The main focus of our research is ligand-gated ion channels and glutamate receptors in particular. We are interested in the mechanism of gating, the process that starts with binding of a ligand to the receptor and ends with opening of the ion channel pore for the flow of permeant ions. We try to understand molecular composition of the ion channel gates as well as changes in the ion channel protein associated with gating. We are also interested in the mechanism of ion channel block. Deciphering molecular bases of ion channel block not only helps understanding functional architecture of the ion channel itself but also provides valuable information for the design of new blockers that may become promising drugs in future.
Sobolevsky A. I., Rosconi M. P. and Gouaux E. (2009) X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462: 745–756.
Sobolevsky A. I., Prodromou M. L., Yelshansky M. V. and Wollmuth L. P. (2007) Subunit-specific Contribution of Pore-Forming Domains to NMDA Receptor Channel Structure and Gating. J. Gen. Physiol. 129: 509-525.
Sobolevsky A. I., Yelshansky M. V. and Wollmuth L. P. (2004) The Outer Pore of the Glutamate Receptor Channel has Two-fold Rotational Symmetry. Neuron 41: 367-378.
Sobolevsky A. I., Beck C. and Wollmuth L. P. (2002) Molecular Rearrangements of the Extracellular Vestibule in NMDAR Channels During Gating. Neuron 33: 75-85.
Sobolevsky A. I. and Yelshansky M. V. (2000) The trapping block of NMDA-receptor channels in acutely isolated rat hippocampal neurones. J. Physiol. 526: 493-506.
Sobolevsky A. I., Koshelev S. G. and Khodorov B. I. (1999) Probing of NMDA channels with fast blockers. J. Neurosci. 19: 10611-10626.