Establishing homology between mitochondrial calcium uniporters, prokaryotic magnesium channels and chlamydial IncA proteins.

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.

[1]  Milton H Saier,et al.  BioV Suite – a collection of programs for the study of transport protein evolution , 2012, The FEBS journal.

[2]  S. Carr,et al.  EMRE Is an Essential Component of the Mitochondrial Calcium Uniporter Complex , 2013, Science.

[3]  T. Hackstadt,et al.  Inhibition of Fusion of Chlamydia trachomatis Inclusions at 32°C Correlates with Restricted Export of IncA , 2002, Infection and Immunity.

[4]  D. Bechhofer,et al.  A tenth atp gene and the conserved atpI gene of a Bacillus atp operon have a role in Mg2+ uptake , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Saier,et al.  Computer-aided analyses of transport protein sequences: gleaning evidence concerning function, structure, biogenesis, and evolution , 1994, Microbiological reviews.

[6]  Dorjee G. Tamang,et al.  Mercury Transport in Bacteria , 2007 .

[7]  T. A. Krulwich,et al.  Roles of AtpI and Two YidC-Type Proteins from Alkaliphilic Bacillus pseudofirmus OF4 in ATP Synthase Assembly and Nonfermentative Growth , 2012, Journal of bacteriology.

[8]  W. Fink.  Microcomputers and Phylogenetic Analysis , 1986, Science.

[9]  V. Mootha,et al.  Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter , 2011, Nature.

[10]  J. Thompson,et al.  The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. , 1997, Nucleic acids research.

[11]  K. Laband,et al.  MCUR1 is an essential component of mitochondrial Ca(2+) uptake that regulates cellular metabolism. , 2013, Nature cell biology.

[12]  G. Myers,et al.  Genome sequencing and comparative analysis of three Chlamydia pecorum strains associated with different pathogenic outcomes , 2014, BMC Genomics.

[13]  J. Felsenstein.  An alternating least squares approach to inferring phylogenies from pairwise distances. , 1997, Systematic biology.

[14]  Jonathan S. Chen,et al.  The Amino Acid-Polyamine-Organocation Superfamily , 2012, Journal of Molecular Microbiology and Biotechnology.

[15]  Roderic D M Page,et al.  Visualizing Phylogenetic Trees Using TreeView , 2003, Current protocols in bioinformatics.

[16]  F. Paumet,et al.  Two Coiled-Coil Domains of Chlamydia trachomatis IncA Affect Membrane Fusion Events during Infection , 2013, PloS one.

[17]  M. Saier,et al.  Multidrug resistance: phylogenetic characterization of superfamilies of secondary carriers that include drug exporters. , 2010, Methods in molecular biology.

[18]  Wilfred W. Li,et al.  MEME: discovering and analyzing DNA and protein sequence motifs , 2006, Nucleic Acids Res..

[19]  I. Ambudkar,et al.  Faculty Opinions recommendation of A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. , 2011 .

[20]  G. Tusnády,et al.  Principles governing amino acid composition of integral membrane proteins: application to topology prediction. , 1998, Journal of molecular biology.

[21]  V. Mootha,et al.  Evolutionary Diversity of the Mitochondrial Calcium Uniporter , 2012, Science.

[22]  P. Pinton,et al.  Mitochondrial calcium uniporter, MiRNA and cancer , 2013, Communicative & integrative biology.

[23]  Y Zhai,et al.  A web-based program (WHAT) for the simultaneous prediction of hydropathy, amphipathicity, secondary structure and transmembrane topology for a single protein sequence. , 2001, Journal of molecular microbiology and biotechnology.

[24]  D. Rockey,et al.  Identification of Concomitant Infection with Chlamydia trachomatis IncA-Negative Mutant and Wild-Type Strains by Genomic, Transcriptional, and Biological Characterizations , 2008, Infection and Immunity.

[25]  Charles Elkan,et al.  The Transporter Classification Database: recent advances , 2008, Nucleic Acids Res..

[26]  P. Pinton,et al.  The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications , 2014, The Journal of physiology.

[27]  K. Katoh,et al.  MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability , 2013, Molecular biology and evolution.

[28]  M. Yen,et al.  Bioinformatic Analyses of Transmembrane Transport: Novel Software for Deducing Protein Phylogeny, Topology, and Evolution , 2009, Journal of Molecular Microbiology and Biotechnology.

[29]  Milton H Saier,et al.  Topological and phylogenetic analyses of bacterial holin families and superfamilies. , 2013, Biochimica et biophysica acta.

[30]  M H Saier,et al.  A web-based program for the prediction of average hydropathy, average amphipathicity and average similarity of multiply aligned homologous proteins. , 2001, Journal of molecular microbiology and biotechnology.

[31]  R F Doolittle,et al.  Convergent evolution: the need to be explicit. , 1994, Trends in biochemical sciences.

[32]  Sumit Arora,et al.  The transporter–opsin–G protein‐coupled receptor (TOG) superfamily , 2013, The FEBS journal.

[33]  Jaehoon Cho,et al.  Phylogenetic Characterization of Transport Protein Superfamilies: Superiority of SuperfamilyTree Programs over Those Based on Multiple Alignments , 2012, Journal of Molecular Microbiology and Biotechnology.

[34]  Can V. Tran,et al.  Phylogeny as a guide to structure and function of membrane transport proteins (Review) , 2004, Molecular membrane biology.

[35]  Milton H. Saier,et al.  Bioinformatic Analyses of Bacterial Mercury Ion (Hg2+) Transporters , 2012, Water, Air, & Soil Pollution.

[36]  M. Saier,et al.  The major facilitator superfamily (MFS) revisited , 2012, The FEBS journal.

[37]  Zhengwei Zhu,et al.  CD-HIT: accelerated for clustering the next-generation sequencing data , 2012, Bioinform..

[38]  W. Fitch,et al.  Construction of phylogenetic trees. , 1967, Science.