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Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA.


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 that co-purified with UapA: phosphatidylcholine, 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 stabilizing 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.

SUBMITTER: Pyle E 

PROVIDER: S-EPMC6058078 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA.

Pyle Euan E   Kalli Antreas C AC   Amillis Sotiris S   Hall Zoe Z   Lau Andy M AM   Hanyaloglu Aylin C AC   Diallinas George G   Byrne Bernadette B   Politis Argyris A  

Cell chemical biology 20180419 7


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 that co-purified with UapA: phosphatidylcholine, phosphatidylethanolamine (PE), and phosphatidylinositol (PI). UapA d  ...[more]

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