title: Phylogenetic and functional analysis of the Cation Diffusion Facilitator (CDF) family: improved signature and prediction of substrate specificity.
abstract: BACKGROUND
  The Cation Diffusion Facilitator (CDF) family is a ubiquitous family of heavy metal transporters. Much interest in this family has focused on implications for human health and bioremediation. In this work a broad phylogenetic study has been undertaken which, considered in the context of the functional characteristics of some fully characterised CDF transporters, has aimed at identifying molecular determinants of substrate selectivity and at suggesting metal specificity for newly identified CDF transporters.
  
  
  RESULTS
  Representative CDF members from all three kingdoms of life (Archaea, Eubacteria, Eukaryotes) were retrieved from genomic databases. Protein sequence alignment has allowed detection of a modified signature that can be used to identify new hypothetical CDF members. Phylogenetic reconstruction has classified the majority of CDF family members into three groups, each containing characterised members that share the same specificity towards the principally-transported metal, i.e. Zn, Fe/Zn or Mn. The metal selectivity of newly identified CDF transporters can be inferred by their position in one of these groups. The function of some conserved amino acids was assessed by site-directed mutagenesis in the poplar Zn2+ transporter PtdMTP1 and compared with similar experiments performed in prokaryotic members. An essential structural role can be assigned to a widely conserved glycine residue, while aspartate and histidine residues, highly conserved in putative transmembrane domains, might be involved in metal transport. The potential role of group-conserved amino acid residues in metal specificity is discussed.
  
  
  CONCLUSIONS
  In the present study phylogenetic and functional analyses have allowed the identification of three major substrate-specific CDF groups. The metal selectivity of newly identified CDF transporters can be inferred by their position in one of these groups. The modified signature sequence proposed in this work can be used to identify new hypothetical CDF members.
authors: UMR INRA/UHP 1136 Interactions Arbres/Micro-organismes, Nancy-Université, Vandoeuvre, France. barbara.montanini@nemo.unipr.it <barbara.montanini@nemo.unipr.it>
authors: Barbara
authors: B
authors: Montanini
authors: Damien
authors: D
authors: Blaudez
authors: Sylvain
authors: S
authors: Jeandroz
authors: Dale
authors: D
authors: Sanders
authors: Michel
authors: M
authors: Chalot
mesh_terms: D001105:Archaea / Q000502:physiology*; D018407:Bacterial Physiological Phenomena; D001692:Biological Transport / Q000235:genetics; D002104:Cadmium / Q000378:metabolism; D027682:Cation Transport Proteins / Q000145:classification* / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D003035:Cobalt / Q000378:metabolism; D017124:Conserved Sequence; D005057:Eukaryotic Cells / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D019216:Metals, Heavy / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D010940:Plant Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D015032:Zinc / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D002412:Cations; D019216:Metals, Heavy; D010940:Plant Proteins; D002104:Cadmium; D003035:Cobalt; D008345:Manganese; D007501:Iron; D015032:Zinc