A study of NaChBac, a sodium channel from Bacillus halodurans, indicates that channel formation requires tetramerization of the protein.
Bacterial ion channels have recently taught us some important lessons on the structure and function of channel proteins from eukaryotic cells, including neurons. First there was KcsA, a bacterial potassium channel that has told us a great deal about the mechanisms of ion selectivity and permeation. Then came GluR0, a prokaryotic glutamate receptor that is permeable to potassium and might represent an evolutionary 'missing link' between ligand- and voltage-gated channels. Enter now NaChBac, a sodium channel from Bacillus halodurans that, surprisingly, is most similar to known voltage-gated calcium channels.
Ren et al. identified NaChBac while searching for homologues of the sperm protein CatSper, an ion channel that is crucial for male fertility. The amino-acid sequence of NaChBac is similar to those of voltage-gated calcium channels, particularly in the pore region. But whereas most voltage-gated calcium (and sodium) channels have 24 transmembrane helices organized in four homologous domains, NaChBac has only six, indicating that channel formation requires tetramerization of the protein.
The authors carried out a thorough biophysical characterization of NaChBac channels, and made a series of surprising observations. First, although the pore sequence resembles that of calcium channels, NaChBac was strongly selective for sodium. Second, although NaChBac is a sodium channel, it was sensitive to blockers of L-type calcium channels. And third, although the bacterial channel was gated by voltage changes, the kinetics of its activation, inactivation and recovery from inactivation were much slower than those of other voltage-gated sodium channels.
The discovery of NaChBac tells us that the formation of a sodium channel does not require that the 24 transmembrane domains be present in a single protein molecule; instead, functional channels can assemble from simpler building blocks. So, the identification of NaChBac supports the idea that gene duplications resulted in the appearance of eukaryotic sodium channels. But more importantly, the preference of NaChBac for sodium, despite its similarity to a calcium channel, should lead us to revise our views on the molecular determinants of ion selectivity. It is to be hoped that the discovery of this bacterial channel will foster a better understanding of sodium channels, in the same way that KcsA has aided in the study of potassium channels.
Juan Carlos López
References
ORIGINAL RESEARCH PAPER Ren, D. et al. A prokaryotic voltage-gated sodium channel. Science294, 2372–2375 (2001) | Article | PubMed |
FURTHER READING Catterall, W. A. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron26, 13–25 (2000) | PubMed |
