Structural lipids enable the formation of functional oligomers of the eukaryotic purine symporter UapA

Euan Pyle, Sotiris Amillis, Antreas Kalli, Zoe Hall, Andy Man Chung Lau, Bernadette Byrne , Aylin C. Hanyaloglu, George Diallinas, Anargyros Politis

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Abstract

The role of membrane lipids in modulating eukaryotic transporter assembly and function remains unclear. We investigated the effect of membrane lipids in the structure and transport activity of the purine transporter UapA, from Aspergillus nidulans. We found that UapA exists mainly as a dimer and that two lipid molecules bind per UapA dimer. We identified three phospholipid classes which co-purified with UapA: phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI). UapA delipidation caused dissociation of the dimer into monomers. Subsequent addition of PI or PE rescued the UapA dimer and allowed recovery of bound lipids, suggesting a central role of these lipids in stabilising the dimer. Molecular dynamics simulations predicted a lipid-binding site near the UapA dimer interface. Mutational analyses established that lipid binding at this site is essential for formation of functional UapA dimers. We propose that structural lipids have a central role in the formation of functional, dimeric UapA.
Original languageEnglish
Number of pages14
JournalChemistry and Biology
Early online date19 Apr 2018
DOIs
Publication statusPublished - Apr 2018

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