| Structural highlights
Function
[UAPA_EMENI] Uric acid-xanthine transporter.[1] [2] [3]
Publication Abstract from PubMed
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-G411VDelta1-11) 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.
Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity.,Alguel Y, Amillis S, Leung J, Lambrinidis G, Capaldi S, Scull NJ, Craven G, Iwata S, Armstrong A, Mikros E, Diallinas G, Cameron AD, Byrne B Nat Commun. 2016 Apr 18;7:11336. doi: 10.1038/ncomms11336. PMID:27088252[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Koukaki M, Vlanti A, Goudela S, Pantazopoulou A, Gioule H, Tournaviti S, Diallinas G. The nucleobase-ascorbate transporter (NAT) signature motif in UapA defines the function of the purine translocation pathway. J Mol Biol. 2005 Jul 15;350(3):499-513. PMID:15953615 doi:http://dx.doi.org/10.1016/j.jmb.2005.04.076
- ↑ Goudela S, Karatza P, Koukaki M, Frillingos S, Diallinas G. Comparative substrate recognition by bacterial and fungal purine transporters of the NAT/NCS2 family. Mol Membr Biol. 2005 May-Jun;22(3):263-75. PMID:16096268 doi:http://dx.doi.org/10.1080/09687860500093016
- ↑ Gournas C, Amillis S, Vlanti A, Diallinas G. Transport-dependent endocytosis and turnover of a uric acid-xanthine permease. Mol Microbiol. 2010 Jan;75(1):246-60. doi: 10.1111/j.1365-2958.2009.06997.x. Epub, 2009 Dec 11. PMID:20002879 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.06997.x
- ↑ Alguel Y, Amillis S, Leung J, Lambrinidis G, Capaldi S, Scull NJ, Craven G, Iwata S, Armstrong A, Mikros E, Diallinas G, Cameron AD, Byrne B. Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity. Nat Commun. 2016 Apr 18;7:11336. doi: 10.1038/ncomms11336. PMID:27088252 doi:http://dx.doi.org/10.1038/ncomms11336
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