Crystal Structure of a Pore Only Sodium Channel

Voltage-gated sodium channels (VGSC) are central to neuromuscular physiology generating the leading phase of action potentials in excitable cells. A variety of marine bacteria produce voltage gated sodium channels that share features with eukaryotic VGSCs and voltage-gated calcium channels (VGCCs). These bacterial channels provide tractable subjects for detailed structural analysis of common features that impact VGSC and VGCC selectivity and gating. We previously reported a structural based design approach in which dissection of the ion conducting module of bacterial VGSCs from the voltage sensor domain created a set of stand-alone ‘pore only’ channels (Shaya et al. PNAS 2011). These ‘pore-only’ channels self-assemble as tetramers and form functional, ion selective channels when incorporated into lipid vesicles.Here, we present the crystal structure of a bacterial ‘pore-only’ sodium channel. The structure encompasses both the transmembrane and the cytoplasmic parts of the protein and reveals new features that impact channel assembly, gating, and ion permeation.