Evolutionary relationship between K(+) channels and symporters

Biophys J. 1999 Aug;77(2):775-88. doi: 10.1016/S0006-3495(99)76931-6.


The hypothesis is presented that at least four families of putative K(+) symporter proteins, Trk and KtrAB from prokaryotes, Trk1,2 from fungi, and HKT1 from wheat, evolved from bacterial K(+) channel proteins. Details of this hypothesis 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 determines the ion selectivity (designated P). The symporter sequences appear to contain 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 K(+) channel subunit. The homology of MPM motifs is supported by a statistical comparison of the numerical profiles derived from multiple sequence alignments formed for each protein family. Furthermore, these quantitative results indicate that the KtrAB family of symporters has remained closest to the single-MPM ancestor protein. Strong sequence evidence is also found for homology between the cytoplasmic C-terminus of numerous bacterial K(+) channels and the cytoplasm-resident TrkA and KtrA subunits of the Trk and KtrAB symporters, which in turn are homologous to known dinucleotide-binding domains of other proteins. The case for homology between bacterial K(+) channels and the four families of K(+) symporters is further supported by the accompanying manuscript, in which the patterns of residue conservation are demonstrated to be similar to each other and consistent with the known 3D structure of the KcsA K(+) channel.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites / genetics
  • Biophysical Phenomena
  • Biophysics
  • Carrier Proteins / genetics
  • Cation Transport Proteins*
  • Conserved Sequence
  • Evolution, Molecular*
  • Fungal Proteins / genetics
  • Membrane Proteins / genetics
  • Molecular Sequence Data
  • Oligonucleotides / metabolism
  • Plant Proteins / genetics
  • Potassium Channels / chemistry
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism
  • Protein Conformation
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Streptomyces / genetics
  • Streptomyces / metabolism
  • Symporters*


  • Bacterial Proteins
  • Carrier Proteins
  • Cation Transport Proteins
  • Fungal Proteins
  • HKT1 protein, plant
  • KtrB protein, Bacteria
  • Membrane Proteins
  • Oligonucleotides
  • Plant Proteins
  • Potassium Channels
  • Saccharomyces cerevisiae Proteins
  • Symporters
  • prokaryotic potassium channel
  • TRK1 protein, S cerevisiae