The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily.

The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily (TC #2.A.66) consists of four previously recognized families: (a) the ubiquitous multi-drug and toxin extrusion (MATE) family; (b) the prokaryotic polysaccharide transporter (PST) family; (c) the eukaryotic oligosaccharidyl-lipid flippase (OLF) family and (d) the bacterial mouse virulence factor family (MVF). Of these four families, only members of the MATE family have been shown to function mechanistically as secondary carriers, and no member of the MVF family has been shown to function as a transporter. Establishment of a common origin for the MATE, PST, OLF and MVF families suggests a common mechanism of action as secondary carriers catalyzing substrate/cation antiport. Most protein members of these four families exhibit 12 putative transmembrane alpha-helical segments (TMSs), and several have been shown to have arisen by an internal gene duplication event; topological variation is observed for some members of the superfamily. The PST family is more closely related to the MATE, OLF and MVF families than any of these latter three families are related to each other. This fact leads to the suggestion that primordial proteins most closely related to the PST family were the evolutionary precursors of all members of the MOP superfamily. Here, phylogenetic trees and average hydropathy, similarity and amphipathicity plots for members of the four families are derived and provide detailed evolutionary and structural information about these proteins. We show that each family exhibits unique characteristics. For example, the MATE and PST families are characterized by numerous paralogues within a single organism (58 paralogues of the MATE family are present in Arabidopsis thaliana), while the OLF family consists exclusively of orthologues, and the MVF family consists primarily of orthologues. Only in the PST family has extensive lateral transfer of the encoding genes occurred, and in this family as well as the MVF family, topological variation is a characteristic feature. The results serve to define a large superfamily of transporters that we predict function to export substrates using a monovalent cation antiport mechanism.

[1]  I S Roberts,et al.  Structure, assembly and regulation of expression of capsules in Escherichia coli , 1999, Molecular microbiology.

[2]  S. Schuldiner,et al.  A model for coupling of H(+) and substrate fluxes based on "time-sharing" of a common binding site. , 2000, Biochemistry.

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

[4]  G. Fink,et al.  Arabidopsis ALF5, a Multidrug Efflux Transporter Gene Family Member, Confers Resistance to Toxins , 2001, The Plant Cell Online.

[5]  M H Saier,et al.  The drug/metabolite transporter superfamily. , 2001, European journal of biochemistry.

[6]  T. Tsuchiya,et al.  NorM of Vibrio parahaemolyticus Is an Na+-Driven Multidrug Efflux Pump , 2000, Journal of bacteriology.

[7]  Erik L. L. Sonnhammer,et al.  A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences , 1998, ISMB.

[8]  D. Kahn,et al.  glnD and mviN Are Genes of an Essential Operon in Sinorhizobium meliloti , 2001, Journal of bacteriology.

[9]  J. Claverys,et al.  Competence‐specific induction of recA is required for full recombination proficiency during transformation in Streptococcus pneumoniae , 1998, Molecular microbiology.

[10]  William R. Jacobs,et al.  Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice , 1999, Nature.

[11]  I. Paulsen,et al.  The multidrug efflux protein NorM is a prototype of a new family of transporters , 1999, Molecular microbiology.

[12]  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.

[13]  L. Burrows,et al.  Genetics of O-Antigen Biosynthesis inPseudomonas aeruginosa , 1999, Microbiology and Molecular Biology Reviews.

[14]  H. Fukuda,et al.  Improvement of S-adenosylmethionine production by integration of the ethionine-resistance gene into chromosomes of the yeast Saccharomyces cerevisiae , 2004, Applied Microbiology and Biotechnology.

[15]  Milton H. Saier,et al.  Size Comparisons among Integral Membrane Transport Protein Homologues in Bacteria, Archaea, and Eucarya , 2001, Journal of bacteriology.

[16]  Thomas L. Madden,et al.  BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences. , 1999, FEMS microbiology letters.

[17]  Can V. Tran,et al.  Web-Based Programs for the Display and Analysis of Transmembrane α-Helices in Aligned Protein Sequences , 2003, Journal of Molecular Microbiology and Biotechnology.

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

[19]  Kutsukake Kazuhiro,et al.  Sequence analysis of the flgA gene and its adjacent region in Salmonella typhimurium, and identification of another flagellar gene, flgN , 1994 .

[20]  M H Saier,et al.  Microbial genome analyses: global comparisons of transport capabilities based on phylogenies, bioenergetics and substrate specificities. , 1998, Journal of molecular biology.

[21]  Hideyuki Suzuki,et al.  Functional Analysis of the Erwinia herbicola tutB Gene and Its Product , 2002, Journal of bacteriology.

[22]  W. Konings,et al.  Drug efflux proteins in multidrug resistant bacteria. , 1997, Biological chemistry.

[23]  William Saurin,et al.  Getting In or Out: Early Segregation Between Importers and Exporters in the Evolution of ATP-Binding Cassette (ABC) Transporters , 1999, Journal of Molecular Evolution.

[24]  S. Salzberg,et al.  Evidence for lateral gene transfer between Archaea and Bacteria from genome sequence of Thermotoga maritima , 1999, Nature.

[25]  P. Reeves,et al.  Extensive Variation in the O-Antigen Gene Cluster within One Salmonella enterica Serogroup Reveals an Unexpected Complex History , 2002, Journal of bacteriology.

[26]  J. Chen,et al.  VmrA, a Member of a Novel Class of Na+-Coupled Multidrug Efflux Pumps from Vibrio parahaemolyticus , 2002, Journal of bacteriology.

[27]  E. Dassa,et al.  The ABC of ABCS: a phylogenetic and functional classification of ABC systems in living organisms. , 2001, Research in microbiology.

[28]  M. Pallen RpoN‐dependent transcription of rpoH? , 1999, Molecular microbiology.

[29]  Milton H. Saier Jr.,et al.  An Automated Program to Screen Databases for Members of Protein Families , 2003, Journal of Molecular Microbiology and Biotechnology.

[30]  M. Saier,et al.  TRAP transporters: an ancient family of extracytoplasmic solute-receptor-dependent secondary active transporters. , 1999, Microbiology.

[31]  K. Nelson,et al.  Comparative genomics of microbial drug efflux systems. , 2001, Journal of molecular microbiology and biotechnology.

[32]  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.

[33]  Chris Sander,et al.  Removing near-neighbour redundancy from large protein sequence collections , 1998, Bioinform..

[34]  J. Devereux,et al.  A comprehensive set of sequence analysis programs for the VAX , 1984, Nucleic Acids Res..

[35]  G. Heijne Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. , 1992, Journal of molecular biology.

[36]  T. Tsuchiya,et al.  Na+-driven multidrug efflux pump VcmA from Vibrio cholerae non-O1, a non-halophilic bacterium , 2001 .

[37]  I. Paulsen,et al.  Major Facilitator Superfamily , 1998, Microbiology and Molecular Biology Reviews.

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

[39]  M H Saier,et al.  Computer-based analyses of the protein constituents of transport systems catalysing export of complex carbohydrates in bacteria. , 1997, Microbiology.

[40]  A. Driessen,et al.  Mechanisms of multidrug transporters. , 1997, FEMS microbiology reviews.

[41]  M. Saier,et al.  CHR, a Novel Family of Prokaryotic Proton Motive Force-Driven Transporters Probably Containing Chromate/Sulfate Antiporters , 1998, Journal of bacteriology.

[42]  F. Yoshimura,et al.  A MATE Family Multidrug Efflux Transporter Pumps out Fluoroquinolones in Bacteroides thetaiotaomicron , 2001, Antimicrobial Agents and Chemotherapy.

[43]  Roderic D. M. Page,et al.  TreeView: an application to display phylogenetic trees on personal computers , 1996, Comput. Appl. Biosci..

[44]  Yufeng Zhai,et al.  A simple sensitive program for detecting internal repeats in sets of multiply aligned homologous proteins. , 2002, Journal of molecular microbiology and biotechnology.

[45]  C. Woese,et al.  Were the original eubacteria thermophiles? , 1987, Systematic and applied microbiology.

[46]  M H Saier,et al.  Phylogenetic characterization of novel transport protein families revealed by genome analyses. , 1999, Biochimica et biophysica acta.

[47]  M H Saier,et al.  Phylogeny of multidrug transporters. , 2001, Seminars in cell & developmental biology.

[48]  W. Wackernagel,et al.  Regulatory role of recF in the SOS response of Escherichia coli: impaired induction of SOS genes by UV irradiation and nalidixic acid in a recF mutant , 1987, Journal of bacteriology.

[49]  M H Saier,et al.  A new subfamily of bacterial ABC‐type transport systems catalyzing export of drugs and carbohydrates , 1992, Protein science : a publication of the Protein Society.

[50]  I. Paulsen,et al.  Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes. , 2000, Journal of molecular biology.

[51]  A. Cozzone,et al.  Cells of Escherichia coli Contain a Protein-Tyrosine Kinase, Wzc, and a Phosphotyrosine-Protein Phosphatase, Wzb , 1999, Journal of bacteriology.

[52]  M. O. Dayhoff,et al.  Establishing homologies in protein sequences. , 1983, Methods in enzymology.

[53]  W. Pearson Rapid and sensitive sequence comparison with FASTP and FASTA. , 1990, Methods in enzymology.

[54]  M. Pagni,et al.  Teichuronic acid operon of Bacillus subtilis 168 , 1999, Molecular microbiology.

[55]  P. Reeves,et al.  Evolution of Salmonella O antigen variation by interspecific gene transfer on a large scale. , 1993, Trends in genetics : TIG.

[56]  H. Nikaido Multidrug efflux pumps of gram-negative bacteria , 1996, Journal of bacteriology.

[57]  William Noble Grundy,et al.  Meta-MEME: motif-based hidden Markov models of protein families , 1997, Comput. Appl. Biosci..

[58]  M H Saier,et al.  The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins. , 1999, Journal of molecular microbiology and biotechnology.

[59]  Peter Walter,et al.  Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein , 2002, Nature.

[60]  Yufeng Zhai,et al.  A web-based Tree View (TV) program for the visualization of phylogenetic trees. , 2002, Journal of molecular microbiology and biotechnology.

[61]  Tohru Mizushima,et al.  NorM, a Putative Multidrug Efflux Protein, of Vibrio parahaemolyticus and Its Homolog in Escherichia coli , 1998, Antimicrobial Agents and Chemotherapy.

[62]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[63]  D. Gowda,et al.  Glycobiology of Plasmodium falciparum. , 2001, Biochimie.

[64]  A. Yamaguchi,et al.  Analysis of a Complete Library of Putative Drug Transporter Genes in Escherichia coli , 2001, Journal of bacteriology.

[65]  Yufeng Zhai,et al.  Protein-translocating outer membrane porins of Gram-negative bacteria. , 2002, Biochimica et biophysica acta.