Peng Yuan
Ph.D. University of Pennsylvania
Biochemistry and Molecular Biophysics
I am interested in the structure and function of the eukaryotic SLO family of K+ channels including large-conductance Ca2+- (BK channels, SLO1), Na+-activated (SLO2) K+ channels, and proton-inhibited (SLO3) K+ channels. The voltage- and ligand-gated SLO channels are crucial to human physiology because they participate in a vast array of cellular processes including neuronal excitability, insulin secretion, and skeletal and smooth muscle contractility. In particular, BK channels are negative-feedback regulators linking electrical excitation (membrane voltage) and Ca2+ signaling. Dysfunction of BK channels leads to diseases such as asthma, hypertension, and epilepsy.
The activation of SLO channels by intracellular ligands is conferred by the large cytoplasmic domain, which forms a gating ring structure. Using X-ray crystallography and electrophysiology, my studies have led to a molecular basis for Ca2+ activation of BK channels and suggest new possibilities for targeting the gating ring to treat diseases such as asthma and hypertension (Yuan et al., Science 2010; Yuan et al., Nature 2012). Currently, we are trying to achieve the crystal structure of an entire channel including the voltage sensor domain, the ion-conduction pore, and the intracellular gating ring (a model of the channel is illustrated in figure below).
