A Superfamily of Voltage-gated Sodium Channels in Bacteria*

NaChBac, a six-α-helical transmembrane-spanning protein cloned from Bacillus halodurans, is the first functionally characterized bacterial voltage-gated Na+-selective channel (Ren, D., Navarro, B., Xu, H., Yue, L., Shi, Q., and Clapham, D. E. (2001) Science 294, 2372-2375). As a highly expressing ion channel protein, NaChBac is an ideal candidate for high resolution structural determination and structure-function studies. The biological role of NaChBac, however, is still unknown. In this report, another 11 structurally related bacterial proteins are described. Two of these functionally expressed as voltage-dependent Na+ channels (NaVPZ from Paracoccus zeaxanthinifaciens and NaVSP from Silicibacter pomeroyi). NaVPZ and NaVSP share ∼40% amino acid sequence identity with NaChBac. When expressed in mammalian cell lines, both NaVPZ and NaVSP were Na+-selective and voltage-dependent. However, their kinetics and voltage dependence differ significantly. These single six-α-helical transmembrane-spanning subunits constitute a widely distributed superfamily (NaVBac) of channels in bacteria, implying a fundamental prokaryotic function. The degree of sequence homology (22-54%) is optimal for future comparisons of NaVBac structure and function of similarity and dissimilarity among NaVBac proteins. Thus, the NaVBac superfamily is fertile ground for crystallographic, electrophysiological, and microbiological studies.