Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783341632265912320 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6058078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT pyleeuan structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT kalliantreasc structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT amillissotiris structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT hallzoe structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT lauandym structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT hanyalogluaylinc structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT diallinasgeorge structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT byrnebernadette structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa AT politisargyris structurallipidsenabletheformationoffunctionaloligomersoftheeukaryoticpurinesymporteruapa |