Analysis of sequence divergence in mammalian abcgs predicts a structural network of residues that underlies functional divergence

Mitchell-White, James I.; Stockner, Thomas; Holliday, Nicholas; Briddon, Stephen J.; Kerr, Ian D.

Abstract

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.

Citation

Mitchell-White, J. I., Stockner, T., Holliday, N., Briddon, S. J., & Kerr, I. D. (2021). Analysis of sequence divergence in mammalian abcgs predicts a structural network of residues that underlies functional divergence. International Journal of Molecular Sciences, 22(6), 1-16. https://doi.org/10.3390/ijms22063012

• Journal Article Type: Article
• Acceptance Date: Mar 12, 2021
• Online Publication Date: Mar 16, 2021
• Publication Date: Mar 16, 2021
• Deposit Date: Mar 17, 2021
• Publicly Available Date: Mar 17, 2021
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 6
• Article Number: 3012
• Pages: 1-16
• DOI: https://doi.org/10.3390/ijms22063012
• Keywords: Physical and Theoretical Chemistry; Inorganic Chemistry; Organic Chemistry; Spectroscopy; Molecular Biology; Catalysis; General Medicine; Computer Science Applications
• Public URL: https://nottingham-repository.worktribe.com/output/5399995
• Publisher URL: https://www.mdpi.com/1422-0067/22/6/3012