IAN KERR ian.kerr@nottingham.ac.uk
Associate Professor
Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences
Kerr, Ian; Haider, Ameena J.; Cox, Megan H.; Jones, Natalie; Goode, Alice J.; Bridge, Katherine S.; Wong, Kelvin; Briggs, Deborah
Authors
Ameena J. Haider
Megan H. Cox
Natalie Jones
Alice J. Goode
Katherine S. Bridge
Kelvin Wong
Deborah Briggs
Abstract
ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which it recognizes and transports diverse drugs are important areas of research. In the current study, we have made a series of single amino acid mutations in ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for cell surface expression and function. One mutant (I573A) showed disrupted glycosylation and reduced trafficking kinetics. In contrast with many ABC transporter folding mutations which appear to be ‘rescued’ by chemical chaperones or low temperature incubation, the I573A mutation was not enriched at the cell surface by either treatment, with the majority of the protein being retained in the endoplasmic reticulum (ER). Two other mutations (P485A and M549A) showed distinct effects on transport of ABCG2 substrates reinforcing the role of TM helix 3 in drug recognition and transport and indicating the presence of intracellular coupling regions in ABCG2.
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 17, 2015 |
Publication Date | Aug 22, 2015 |
Deposit Date | Sep 29, 2017 |
Publicly Available Date | Nov 19, 2018 |
Print ISSN | 0144-8463 |
Electronic ISSN | 1573-4935 |
Publisher | Portland Press |
Peer Reviewed | Peer Reviewed |
Volume | 35 |
Issue | 4 |
Article Number | e00241 |
DOI | https://doi.org/10.1042/BSR20150150 |
Public URL | https://nottingham-repository.worktribe.com/output/1118649 |
Publisher URL | http://www.bioscirep.org/content/35/4/e00241 |
PMID | 26294421 |
Files
Haider BiosciRep 2015
(908 Kb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/3.0/
You might also like
Dimerization of ABCG2 analysed by bimolecular fluorescence complementation
(2011)
Journal Article
Long-term exposure to irinotecan reduces cell migration in glioma cells.
(2016)
Journal Article
The multidrug transporter ABCG2: still more questions than answers
(2016)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search