Ming Zhou, Ph.D.Assistant Professor, Physiology & Cellular Biophysics
Tel +1 212-342-3722
Area of Research
Biophysics and physiology of ion channel modulations.
Voltage-dependent potassium channels (Kv) are integral membrane proteins that, in response to membrane voltage change, catalyze K+ to diffuse across the cell membrane. Kv channels are essential to many physiological processes such as the rhythmic beating of the heart, the communication between neurons, and the secretion of hormones. One of the most exciting and important topics in ion channel physiology is to understand the precisely controlled opening and closing, i.e., gating, of a channel. In a cell, Kv channels almost always assemble with other proteins and the gating is modulated by the association of these proteins. The focus and long-term goal of our research is to understand structural bases of gating modulation in Kv channels. Since many diseases such as certain forms of seizures, deafness, ataxia, and cardiac arrhythmias, for instance, are directly attributable to Kv channel dysfunction, results from our research will help develop new and safe therapeutic reagents targeting Kv channels.
Currently, we are working on the modulation of Kv1 family channels by the associated beta subunit (Kvβ). The amino acid sequence of Kvβ is related to oxidoreductases, and the three-dimensional structure of Kvβ shows the canonical structural fold of an oxidoreductase, a cofactor (NADPH) bound, and all the conserved catalytic residues in the right geometry for catalysis to happen. Deletion of Kvβ gene in the fly and mouse causes phenotypes similar to channel deletions. In human, loss of Kvβ gene has been linked to epilepsy and seizure. The physiological function of Kvβ remains unresolved, however. Is Kvβ really an enzyme? If it is, does the enzymatic reaction affect channel gating, or vice versa? To address these questions, we use a multidisciplinary approach, combining electrical recordings of channel function with protein biochemistry and X-ray crystallography.
Weng J, Cao Y., Moss, N., Zhou, M. (2006). Modulation of voltage-dependent Shaker family potassium channels by an aldo-keto reductase. J. Biol. Chem., 281: 15194-15200.
Zhou, M., MacKinnon, R. (2004). A mutant KcsA K+ channel with altered conduction properties and selectivity filter ion distribution. J. Mol. Biol., 338: 839-46
Zhou, M., Morais-Cabral, J., Mann, S., MacKinnon, R. (2001). Potassium channel receptor site for the inactivation gate and quaternary amine blockers. Nature, 411: 657-661.
Gulbis, J, Zhou, M, Mann, S, MacKinnon, R. (2000). Structure of the cytoplasmic β subunit-T1 assembly of voltage-dependent K channels. Science, 289: 123-127
Grosman, C., Zhou, M., Auerbach, A. (2000). Mapping the conformational wave of acetylcholine receptor channel gating. Nature, 403: 773-776.