Structure of a bacterial voltage-gated sodiumchannel pore reveals mechanisms of openingand closing

摘要

Voltage-gated sodium channels are vital membrane proteins essential for electrical signalling;in humans, they are key targets for the development of pharmaceutical drugs. Here we reportthe crystal structure of an open-channel conformation of NavMs, the bacterial channel porefrom the marine bacterium Magnetococcus sp. (strain MC-1). It differs from the recentlypublished crystal structure of a closed form of a related bacterial sodium channel (NavAb) byhaving its internal cavity accessible to the cytoplasmic surface as a result of a bend/rotationabout a central residue in the carboxy-terminal transmembrane segment. This produces anopen activation gate of sufficient diameter to allow hydrated sodium ions to pass through.Comparison of the open and closed structures provides new insight into the features of thefunctional states present in the activation cycles of sodium channels and the mechanism ofchannel opening and closing.