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Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity.

Yilmaz AlguelSotiris AmillisJames LeungGeorge LambrinidisStefano CapaldiNicola J ScullGregory CravenSo IwataAlan ArmstrongEmmanuel MikrosGeorge DiallinasAlexander D CameronBernadette Byrne
Published in: Nature communications (2016)
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.
Keyphrases
  • uric acid
  • metabolic syndrome
  • dna damage
  • mass spectrometry
  • dna repair
  • ionic liquid
  • molecular dynamics simulations
  • molecularly imprinted
  • crystal structure