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

Significance Bacterial voltage-gated sodium channels serve as models of their vertebrate counterparts because they have similar functional components in a simpler structure. We present high-resolution structures of tightly closed and open states. In the closed state, the activation gate fully occludes the conduction pathway, and the intracellular C-terminal domain is revealed as a long four-helix bundle. In the open state, the activation gate has an orifice of ∼10 Å. Molecular dynamics simulations confirm that this conformation would allow permeation of hydrated Na + . These structures are significant advances because they provide a complete closed–open–inactivated conformational cycle in a single voltage-gated sodium channel and give insight into the structural basis for state-dependent binding of sodium channel-blocking drugs.

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