Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/ijms22063012
Keywords
ABC transporter; multidrug resistance; membrane protein; functional divergence; ABCG2
Funding
- BBSRC [BB/S001611/1]
- BBSRC [BB/S001611/1] Funding Source: UKRI
Ask authors/readers for more resources
Members of the mammalian G subfamily of ATP-binding cassette transporters exhibit significant differences in substrate specificity, with ABCG2 playing a crucial role in multidrug resistance due to its wide substrate specificity. Analysis of conservation differences between members in a multiple sequence alignment of ABCG sequences from mammals reveals possible explanations for functional differences. Mapping sets of residues onto the 3D structure of ABCG2 illustrates a network of residues that may confer additional conformational flexibility, allowing for transport of a wider array of substrates.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available