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

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Title: Structural lipids enable the formation of Ffnctional oligomers of the eukaryotic purine symporter UapA
Authors: Pyle, E
Kalli, AC
Amillis, S
Hall, Z
Lau, AM
Hanyaloglu, AC
Diallinas, G
Byrne, B
Politis, A
Item Type: Journal Article
Publication Date: 2018-04-26T11:07:19Z
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.
Issue Date: 10-Apr-2018
Date of Acceptance: 22-Mar-2018
URI: http://hdl.handle.net/10044/1/58702
DOI: https://dx.doi.org/10.1016/j.chembiol.2018.03.011
ISSN: 2451-9456
Publisher: Elsevier
Journal / Book Title: Cell Chemical Biology
Copyright Statement: © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/).
Keywords: UapA
eukaryotic membrane protein
in vivo mutational analyses
ion-mobility mass spectrometry
lipidomics
liquid chromatography-mass spectrometry
membrane protein oligomerization
molecular dynamics simulations
native mass spectrometry
protein-lipid interactions
UapA
eukaryotic membrane protein
in vivo mutational analyses
ion-mobility mass spectrometry
lipidomics
liquid chromatography-mass spectrometry
membrane protein oligomerization
molecular dynamics simulations
native mass spectrometry
protein-lipid interactions
Publication Status: Published online
Conference Place: United States
metadata.pubs.date.publish-online: 2018-04-19
Appears in Collections:Division of Surgery
Faculty of Natural Sciences



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