Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity
| Autor: | Alguel, Yilmaz, Amillis, Sotiris, Leung, James, Lambrinidis, George, Capaldi, Stefano, Scull, Nicola J., Craven, Gregory, Iwata, So, Armstrong, Alan, Mikros, Emmanuel, Diallinas, George, Cameron, Alexander, Byrne, Bernadette |
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| Rok vydání: | 2015 |
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Molecular Science Gene Expression purine transporter Saccharomyces cerevisiae Crystallography X-Ray Xanthine Aspergillus nidulans Protein Structure Secondary Article Substrate Specificity Fungal Proteins membrane protein structure QH Membrane Transport Proteins Biological Transport Recombinant Proteins Protein Structure Tertiary Kinetics purine/H+ symporter UapA purine/H+ symporter membrane protein structure purine transporter Aspergillus nidulans Mutation Thermodynamics Protein Multimerization Protons UapA |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-9 (2016) |
| ISSN: | 2041-1723 |
| Popis: | 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. UapA is a uric acid/xanthine H+ symporter from a filamentous fungus. Here, the authors solve the crystal structure of the transporter in complex with xanthine revealing it to be a dimer, and this homodimerisation is proposed to be important for function. |
| Databáze: | OpenAIRE |
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