Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27088252.
- Also identified by DOI 10.1038/ncomms11336 and PMC identifier 4837479.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Aspergillus nidulans
- Fungal Proteins
- Membrane Transport Proteins
- Protons
- Xanthine