Τίτλος:
Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Alguel, Y.
Amillis, S.
Leung, J.
Lambrinidis, G.
Capaldi, S.
Scull, N.J.
Craven, G.
Iwata, S.
Armstrong, A.
Mikros, E.
Diallinas, G.
Cameron, A.D.
Byrne, B.
Περιοδικό:
Nature Communications
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
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
