Seminar:    (352) Structural Investigation of the Voltage-gated Calcium Channel Cav1.1

Speaker:    Dr. Jianping Wu, Princeton University, USA

Time:        2019-04-18 15:00 to 2019-04-18 16:00

Venue:        Meeting room (406), Building 24

Organizer:    SPST

Abstract:

Voltage-gated calcium (Cav) channels are important membrane proteins that mediate calcium influx upon action potential. They are involved in a variety of physiological processes, such as muscle contraction, hormone secretion, synaptic transmission and gene expression. Malfunction of Cav channels are associated with many neurological and cardiovascular diseases. Therefore, Cav channels are very important drug targets. In fact, several clinical drugs targeted on Cav1 channels have already been widely used for treatment of hypertension. Cav1.1 was the first identified among the 10 Cav channels in mammals and it plays an essential role during excitation-contraction (E-C) coupling duringskeletal muscle contraction. In the past few years, we were focusing on the structural investigation on Cav1.1. We sought an innovative strategy to purify the large protein complex form endogenous tissue. Using single particle cryo-EM, we solved the structure of Cav1.1, which was the first high resolution structure of a eukaryotic Cav channel. The structure helped explaining the subunits assembly, ion selectivity, electro-mechanical coupling of Cav channels. By combining the study on another ion channel RyR1, we also proposed a working model for EC-coupling in skeletal muscle. Recently, we also solved the structures of Cav1.1 in complex with multiple clinical drugs. These structures elucidate the structural basis for specific drug recognition and will provide important framework for future drug developments.

Brief biography of the speaker:Dr. Jianping Wu is currently a postdoc fellow in Nieng Yan’s Lab in the Department of Molecular Biology at Princeton University, USA. He got his BS and Ph.D. degree in School of Life Sciences at Tsinghua University, China in 2012 and 2017, respectively. Jianping Wu’s research interest focuses on structural investigations of important ion channels and transporters. He has published 10 papers as first or co-first author, with 7 of these in Cell, Nature, or Science. He was awarded the Ray Wu Prize in 2017. Jianping is going to set up his own lab in 2019 and will work on structural and mechanistic study of many exciting membrane proteins using multiply technologies, including X-ray crystallography, cryo-electron microscopy (cryo-EM), and cryo-electron tomography (cryo-ET). Students who are interested are welcome to join the new lab!