TY - JOUR
TI - Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity
AU - Alguel, Y.
AU - Amillis, S.
AU - Leung, J.
AU - Lambrinidis, G.
AU - Capaldi, S.
AU - Scull, N.J.
AU - Craven, G.
AU - Iwata, S.
AU - Armstrong, A.
AU - Mikros, E.
AU - Diallinas, G.
AU - Cameron, A.D.
AU - Byrne, B.
JO - Nature Communications
PY - 2016
VL - 7
TODO - null
SP - null
PB - Nature Publishing Group
SN - 2041-1723
TODO - 10.1038/ncomms11336
TODO - 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
TODO - 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.
ER -