Evolutionary relationship between K+ channels and symporters

The hypothesis is presented that at least four families of putative K+ symp orter proteins, Trk and KtrAB from prokaryotes, Trk1,2 from fungi, and HKT1 from wheat, evolved from bacterial K+ channel proteins. Details of this hy pothesis are organized around the recently determined crystal structure of a bacterial K+ channel: i.e., KcsA from Streptomyces lividans. Each of the four identical subunits of this channel has two fully transmembrane helices (designated M1 and M2), plus an intervening hairpin segment that determine s the ion selectivity (designated P). The symporter sequences appear to con tain four sequential M1-P-M2 motifs (MPM), which are likely to have arisen from gene duplication and fusion of the single MPM motif of a bacterial Kchannel subunit. The homology of MPM motifs is supported by a statistical c omparison of the numerical profiles derived from multiple sequence alignmen ts formed for each protein family. Furthermore, these quantitative results indicate that the KtrAB family of symporters has remained closest to the si ngle-MPM ancestor protein. Strong sequence evidence is also found for homol ogy between the cytoplasmic C-terminus of numerous bacterial K+ channels an d the cytoplasm-resident TrkA and KtrA subunits of the Trk and KtrAB sympor ters, which in turn are homologous to known dinucleotide-binding domains of other proteins. The case for homology between bacterial K+ channels and th e four families of K+ symporters is further supported by the accompanying m anuscript, in which the patterns of residue conservation are demonstrated t o be similar to each other and consistent with the known 3D structure of th e KcsA K+ channel.