Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel.

ABSTRACT: Voltage-gated sodium (Na_V) channels initiate action potentials in nerve, muscle, and other electrically excitable cells. The structural basis of voltage gating is uncertain because the resting state exists only at deeply negative membrane potentials. To stabilize the resting conformation, we inserted voltage-shifting mutations and introduced a disulfide crosslink in the VS of the ancestral bacterial sodium channel Na_VAb. Here, we present a cryo-EM structure of the resting state and a complete voltage-dependent gating mechanism. The S4 segment of the VS is drawn intracellularly, with three gating charges passing through the transmembrane electric field. This movement forms an elbow connecting S4 to the S4-S5 linker, tightens the collar around the S6 activation gate, an

SUBMITTER: Wisedchaisri G 

PROVIDER: S-EPMC6688928 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature