A superfamily of voltage-gated sodium channels in bacteria

NaChBac, a six-alpha-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 (Na(V)PZ from Paracoccus zeaxanthinifaciens and NaVSP from Silicibacter pomeroyi). Na(V)PZ and NaVSP share similar to40% amino acid sequence identity with NaChBac. When expressed in mammalian cell lines, both Na(V)PZ and NaVSP were Na+-selective and voltage-dependent. However, their kinetics and voltage dependence differ significantly. These single six-alpha-helical transmembrane-spanning subunits constitute a widely distributed superfamily (Na(V)Bac) of channels in bacteria, implying a fundamental prokaryotic function. The degree of sequence homology (22 - 54%) is optimal for future comparisons of Na(V)Bac structure and function of similarity and dissimilarity among Na(V)Bac proteins. Thus, the Na(V)Bac superfamily is fertile ground for crystallographic, electrophysiological, and microbiological studies.