title: Establishing homology between mitochondrial calcium uniporters, prokaryotic magnesium channels and chlamydial IncA proteins.
abstract: Mitochondrial calcium uniporters (MCUs) (TC no. 1.A.77) are oligomeric channel proteins found in the mitochondrial inner membrane. MCUs have two well-conserved transmembrane segments (TMSs), connected by a linker, similar to bacterial MCU homologues. These proteins and chlamydial IncA proteins (of unknown function; TC no. 9.B.159) are homologous to prokaryotic Mg(2+) transporters, AtpI and AtpZ, based on comparison scores of up to 14.5 sds. A phylogenetic tree containing all of these proteins showed that the AtpZ proteins cluster coherently as a subset within the large and diverse AtpI cluster, which branches separately from the MCUs and IncAs, both of which cluster coherently. The MCUs and AtpZs share the same two TMS topology, but the AtpIs have four TMSs, and IncAs can have either two (most frequent) or four (less frequent) TMSs. Binary alignments, comparison scores and motif analyses showed that TMSs 1 and 2 align with TMSs 3 and 4 of the AtpIs, suggesting that the four TMS AtpI proteins arose via an intragenic duplication event. These findings establish an evolutionary link interconnecting eukaryotic and prokaryotic Ca(2+) and Mg(2+) transporters with chlamydial IncAs, and lead us to suggest that all members of the MCU superfamily, including IncAs, function as divalent cation channels.
authors.affiliation: Department of Molecular Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
authors.forename: Ake
authors.initials: A
authors.lastname: Vastermark
authors.affiliation: Department of Molecular Biology, University of California at San Diego, La Jolla, CA 92093-0116, USA.
authors.forename: Milton H
authors.initials: MH
authors.lastname: Saier
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000737:chemistry / Q000145:classification / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D019143:Evolution, Molecular; D008274:Magnesium / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D015220:Calcium Channels; D027682:Cation Transport Proteins; C460868:IncA protein, Chlamydia trachomatis; D008565:Membrane Proteins; C034703:mitochondrial calcium uniporter; D008274:Magnesium; D002118:Calcium