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

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...

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Autores principales: Pyle, Euan, Kalli, Antreas C., Amillis, Sotiris, Hall, Zoe, Lau, Andy M., Hanyaloglu, Aylin C., Diallinas, George, Byrne, Bernadette, Politis, Argyris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058078/
https://www.ncbi.nlm.nih.gov/pubmed/29681524
http://dx.doi.org/10.1016/j.chembiol.2018.03.011
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author Pyle, Euan
Kalli, Antreas C.
Amillis, Sotiris
Hall, Zoe
Lau, Andy M.
Hanyaloglu, Aylin C.
Diallinas, George
Byrne, Bernadette
Politis, Argyris
author_facet Pyle, Euan
Kalli, Antreas C.
Amillis, Sotiris
Hall, Zoe
Lau, Andy M.
Hanyaloglu, Aylin C.
Diallinas, George
Byrne, Bernadette
Politis, Argyris
author_sort Pyle, Euan
collection PubMed
description 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.
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spelling pubmed-60580782018-07-25 Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA Pyle, Euan Kalli, Antreas C. Amillis, Sotiris Hall, Zoe Lau, Andy M. Hanyaloglu, Aylin C. Diallinas, George Byrne, Bernadette Politis, Argyris Cell Chem Biol Article 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. Cell Press 2018-07-19 /pmc/articles/PMC6058078/ /pubmed/29681524 http://dx.doi.org/10.1016/j.chembiol.2018.03.011 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pyle, Euan
Kalli, Antreas C.
Amillis, Sotiris
Hall, Zoe
Lau, Andy M.
Hanyaloglu, Aylin C.
Diallinas, George
Byrne, Bernadette
Politis, Argyris
Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA
title Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA
title_full Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA
title_fullStr Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA
title_full_unstemmed Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA
title_short Structural Lipids Enable the Formation of Functional Oligomers of the Eukaryotic Purine Symporter UapA
title_sort structural lipids enable the formation of functional oligomers of the eukaryotic purine symporter uapa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058078/
https://www.ncbi.nlm.nih.gov/pubmed/29681524
http://dx.doi.org/10.1016/j.chembiol.2018.03.011
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