@article{3026420,
    title = "Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity",
    author = "Alguel, Y. and Amillis, S. and Leung, J. and Lambrinidis, G. and Capaldi, S. and Scull, N.J. and Craven, G. and Iwata, S. and Armstrong, A. and Mikros, E. and Diallinas, G. and Cameron, A.D. and Byrne, B.",
    journal = "Nature Communications",
    year = "2016",
    volume = "7",
    publisher = "Nature Publishing Group",
    issn = "2041-1723",
    doi = "10.1038/ncomms11336",
    keywords = "bacterial protein;  prestin;  UapA protein;  unclassified drug;  UraA protein;  uracil;  urate transporter;  xanthine;  carrier protein;  fungal protein;  proton;  recombinant protein;  UAPA protein, Aspergillus nidulans;  xanthine, amino acid;  crystal structure;  eukaryote;  fungus;  organic compound;  pigment, amino terminal sequence;  anion exchange;  Article;  Aspergillus nidulans;  binding affinity;  binding site;  cell membrane;  cellular distribution;  complex formation;  conformational transition;  crystal structure;  crystallization;  dimerization;  disulfide bond;  enzyme specificity;  enzyme substrate complex;  heterologous expression;  homodimerization;  molecular dynamics;  nonhuman;  protein binding;  protein conformation;  protein domain;  protein protein interaction;  protein structure;  protein transport;  structure activity relation;  chemistry;  gene expression;  genetics;  kinetics;  metabolism;  molecular model;  mutation;  protein multimerization;  protein secondary structure;  protein tertiary structure;  Saccharomyces cerevisiae;  thermodynamics;  transport at the cellular level;  X ray crystallography, Emericella nidulans;  Eukaryota;  Fungi, Aspergillus nidulans;  Biological Transport;  Crystallography, X-Ray;  Fungal Proteins;  Gene Expression;  Kinetics;  Membrane Transport Proteins;  Models, Molecular;  Mutation;  Protein Multimerization;  Protein Structure, Secondary;  Protein Structure, Tertiary;  Protons;  Recombinant Proteins;  Saccharomyces cerevisiae;  Substrate Specificity;  Thermodynamics;  Xanthine",
    abstract = "The uric acid/xanthine H+ symporter, UapA, is a high-affinity purine transporter from the filamentous fungus Aspergillus nidulans. Here we present the crystal structure of a genetically stabilized version of UapA (UapA-G411VΔ1-11) in complex with xanthine. UapA is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family. The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which was observed to be a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. We postulate that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin."
}