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7179768 
Journal Article 
Establishing homology between mitochondrial calcium uniporters, prokaryotic magnesium channels and chlamydial IncA proteins 
Lee, A; Vastermark, Ake; Saier, MH, Jr; , 
2014 
1 
Microbiology (Reading, England)
ISSN: 1350-0872
EISSN: 1465-2080 
MICROBIOLOGY SOC 
LONDON 
1679-1689 
24869855 
WOS:000341678900012 
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 Mg2+ transporters, Atpl 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 Atpl 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 Atpls 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 Atpls, suggesting that the four TMS Atpl proteins arose via an intragenic duplication event. These findings establish an evolutionary link interconnecting eukaryotic and prokaryotic Ca2+ and Mg2+ transporters with chlamydial IncAs, and lead us to suggest that all members of the MCU superfamily, including IncAs, function as divalent cation channels.