2012年12月21日，清华大学医学院教授颜宁博士应邀访问研究所并举办学术讲座。

2012年12月21日，清华大学医学院教授颜宁博士应邀访问研究所并举办学术讲座。讲座的题目为：Structural Investigation of the voltage-gated sodium channels。张宏博士主持讲座。

Abstract:

Voltage-gated sodium (Nav) channels are essential for the rapid depolarization of nerve and muscle, and are important drug targets. Elucidation of the structures and functional mechanisms of Nav channels will shed light on fundamental ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Nav channels, exemplified by NaChBac (Na+-selective Channel of Bacteria), provides a good model system for structure-function analysis. We recently determined the crystal structure of NavRh, a NaChBac orthologue from marine bacteria alpha proteobacterium HIMB114, at 3.05 Å resolution. The channel comprises an asymmetric tetramer. The carbonyl oxygen atoms of Thr178 and Leu179 constitute an inner site within the selectivity filter (178TLSSWE183) where a hydrated Ca2+ can bind and resides in the crystal structure. The outer mouth of the Na+ selectivity filter, defined by Ser181 and Glu183, is closed, as is the activation gate at the intracellular side of the pore. Molecular dynamics studies revealed the molecular basis for ion selectivity. The voltage sensors adopt a depolarized conformation with all the gating charges exposing to the extracellular side. We hypothesize that NavRh is captured in an inactivated conformation. Comparison of NavRh with NavAb reveals significant conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels.