Sodium-gated ion channels open and close in response to the flow of ions. Here, McCusker et al. report the open structure of a sodium-gated ion channel pore from a bacterial homologue, and show, by comparison with the closed structure, that the movement of a C-terminal helix is sufficient to open the channel.

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The crystal structure of the open conformation of a bacterial voltage-gated sodium channel pore from Magnetococcus sp.(NaVMs) has provided the basis for a molecular dynamics study defining the channel's full ion translocation pathway and conductance process, selectivity, electrophysiological characteristics, and ion-binding sites. Microsecond molecular dynamics simulations permitted a complete time-course characterization of the protein in a membrane system, capturing the plethora of conductance events and revealing a complex mixture of single and multiion phenomena with decoupled rapid bidirectional water transport. The simulations suggest specific localization sites for the sodium ions, which correspond with experimentally determined electron density found in the selectivity filter of the crystal structure. These studies have also allowed us to identify the ion conductance mechanism and its relation to water movement for the NavMs channel pore and to make realistic predictions of its conductance properties. The calculated single-channel conductance and selectivity ratio correspond closely with the electrophysiology measurements of the NavMs channel expressed in HEK 293 cells. The ion translocation process seen in this voltage-gated sodium channel is clearly different from that exhibited by members of the closely related family of voltage-gated potassium channels and also differs considerably from existing proposals for the conductance process in sodium channels. These studies simulate sodium channel conductance based on an experimentally determined structure of a sodium channel pore that has a completely open transmembrane pathway and activation gate. V oltage-gated cation channels are proteins that produce electrical signals in neurons and other excitable cells to regulate muscle contraction, gene expression, and release of hormones and neurotransmitters among other functions. In response to a change in transmembrane electrical potential, the channels open pores through which ions move passively across the membrane. The large family of cation channels includes those selective for sodium, potassium, or calcium. The opening and closing of these ion-specific channels is carefully choreographed to produce the electrical signals required by the nervous system for rapid signal transduction (1).Voltage-gated sodium channels have been causally linked with a wide range of neurological and cardiovascular diseases and hence are important pharmaceutical drug-development targets (2, 3). Eukaryotic voltage-gated sodium channels are large, singlechain polypeptides, consisting of 24 transmembrane (TM) helices that form four homologous repeats, each contributing both a voltage sensor and a pore domain; the latter are arranged to form a central Na + -selective transmembrane pathway. Bacterial voltagegated sodium channels are far simpler, consisting of four polypeptide chains, each of which is composed of six TM segments, with segments TM1-TM4 forming the voltage sensors and TM5-TM6 forming the pore domains. The TM5-TM6 segment...