31EW

UapA (WT) in DDM, Apo state

Summary for 31EW

• Entry DOI: 10.2210/pdb31ew/pdb
• EMDB information: 58351
• Descriptor: Uric acid-xanthine permease, DODECYL-BETA-D-MALTOSIDE, MYRISTIC ACID, ... (8 entities in total)
• Functional Keywords: uapa, ddm, transporter, inward-facing, uric acid, xanthine, membrane protein
• Biological source: Aspergillus nidulans FGSC A4
• Total number of polymer chains: 2
• Total formula weight: 142772.20

Authors

Broutzakis, G.,Gatsogiannis, C. (deposition date: 2026-06-01, release date: 2026-07-01, Last modification date: 2026-07-08)

Primary citation

Broutzakis, G.,Pyrris, Y.,Akrani, I.,Neuhaus, A.,Mikros, E.,Diallinas, G.,Gatsogiannis, C.
Cryo-EM of the eukaryotic purine transporter UapA demonstrates intramolecular and lipid regulation of transport.
Proc.Natl.Acad.Sci.USA, 123:e2513585123-e2513585123, 2026

PubMed Abstract: Members of the nucleobase ascorbate transporter (NAT) family (SLC23) are elevator-type transporters that are responsible for the uptake of nucleobases and ascorbate. In fungi, NAT members are also responsible for the specific uptake of antifungal nucleobase analogues, such as oxypurinol, allopurinol, or 8-azaguanine. Here, we report nearly full-length cryo-EM structures of UapA, a high-affinity purine transporter from the model fungus , in inward-facing apo- and substrate-loaded conformations at 2.06 to 3.5 Å in detergent and lipid nanodiscs. The high-resolution structures reveal the role of water molecules and lipids in substrate binding, specificity, transporter dimerization, and activity. Notably, the N-tail of UapA is found to be structured, interacting with both the core and scaffold domains, which in combination with functional data suggests a dual role in trafficking and transport dynamics. Overall, our study provides unprecedented structural and functional insights into an elevator-type fungal transporter, which may well contribute to the exploitation of NAT transporters as specific gateways for targeted pharmacological antifungal approaches.

PubMed: 42361038
DOI: 10.1073/pnas.2513585123

Experimental method

ELECTRON MICROSCOPY (2.06 Å)