Structures of closed and open states of a voltage-gated sodium channel.

ABSTRACT: Bacterial voltage-gated sodium channels (BacNavs) serve as models of their vertebrate counterparts. BacNavs contain conserved voltage-sensing and pore-forming domains, but they are homotetramers of four identical subunits, rather than pseudotetramers of four homologous domains. Here, we present structures of two Na_VAb mutants that capture tightly closed and open states at a resolution of 2.8-3.2 Å. Introduction of two humanizing mutations in the S6 segment (Na_VAb/FY: T206F and V213Y) generates a persistently closed form of the activation gate in which the intracellular ends of the four S6 segments are drawn tightly together to block ion permeation completely. This construct also revealed the complete structure of the four-helix bundle that forms the C-terminal domain.

SUBMITTER: Lenaeus MJ 

PROVIDER: S-EPMC5393245 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature