Imperial College London


Faculty of Natural SciencesDepartment of Life Sciences

Professor of Molecular Membrane Biology



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BibTex format

author = {Kourkoulou, A and Grevias, P and Lambrinidis, G and Pyle, E and Dionysopoulou, M and Politis, A and Mikros, E and Byrne, B and Diallinas, G},
doi = {10.1101/710897},
journal = {Genetics},
title = {Distinct specific interactions of the UapA transporter with membrane lipids are critical for dimerization, ER-exit and function},
url = {},
year = {2019}

RIS format (EndNote, RefMan)

AB - <jats:title>Abstract</jats:title><jats:p>Transporters are transmembrane proteins that mediate the selective translocation of solutes across biological membranes. Recently, we have shown that specific interactions with plasma membrane phospholipids are essential for formation and/or stability of functional dimers of the purine transporter, UapA, a prototypic eukaryotic member of the ubiquitous NAT family. Here, we show that distinct interactions of UapA with specific or annular lipids are essential for <jats:italic>ab initio</jats:italic> formation of functional dimers in the ER or ER-exit and further subcellular trafficking. Through genetic screens we identify mutations that restore defects in dimer formation and/or trafficking. Suppressors of defective dimerization restore <jats:italic>ab initio</jats:italic> formation of UapA dimers in the ER. Most of these suppressors are located in the movable core domain, but also in the core-dimerization interface and in residues of the dimerization domain exposed to lipids. Molecular Dynamics suggest the majority of suppressors stabilize interhelical interactions in the core domain and thus assist the formation of functional UapA dimers. Among suppressors restoring dimerization, a specific mutation, T401P, was also isolated independently as a suppressor restoring trafficking, suggesting that stabilization of the core domain restores function by sustaining structural defects caused by abolishment of essential interactions with specific or annular lipids. Importantly, introduction of mutations topologically equivalent to T401P into a rat homologue of UapA, namely rSNBT1, permitted the functional expression of a mammalian NAT in <jats:italic>A. nidulans</jats:italic>. Thus, our results provide a potential route for the functional expression and manipulation of mammalian transporters in the model Aspergillus system.</jats:p><jats:sec><jats:title>Author Summar
AU - Kourkoulou,A
AU - Grevias,P
AU - Lambrinidis,G
AU - Pyle,E
AU - Dionysopoulou,M
AU - Politis,A
AU - Mikros,E
AU - Byrne,B
AU - Diallinas,G
DO - 10.1101/710897
PY - 2019///
TI - Distinct specific interactions of the UapA transporter with membrane lipids are critical for dimerization, ER-exit and function
T2 - Genetics
UR -
ER -