Flexible-to-rigid transition is central for substrate transport in the ABC transporter BmrA from Bacillus subtilis

Open access
Date
2019Type
- Journal Article
Citations
Cited 21 times in
Web of Science
Cited 25 times in
Scopus
ETH Bibliography
yes
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Abstract
ATP-binding-cassette (ABC) transporters are molecular pumps that translocate molecules across the cell membrane by switching between inward-facing and outward-facing states. To obtain a detailed understanding of their mechanism remains a challenge to structural biology, as these proteins are notoriously difficult to study at the molecular level in their active, membrane-inserted form. Here we use solid-state NMR to investigate the multidrug ABC transporter BmrA reconstituted in lipids. We identify the chemical-shift differences between the inward-facing, and outward-facing state induced by ATP:Mg2+:Vi addition. Analysis of an X-loop mutant, for which we show that ATPase and transport activities are uncoupled, reveals an incomplete transition to the outward-facing state upon ATP:Mg2+:Vi addition, notably lacking the decrease in dynamics of a defined set of residues observed in wild-type BmrA. This suggests that this stiffening is required for an efficient transmission of the conformational changes to allow proper transport of substrate by the pump. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000361672Publication status
publishedExternal links
Journal / series
Communications BiologyVolume
Pages / Article No.
Publisher
Nature Publishing GroupOrganisational unit
03496 - Meier, Beat H. / Meier, Beat H.
Funding
159707 - NMR studies in the Solid State (SNF)
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Show all metadata
Citations
Cited 21 times in
Web of Science
Cited 25 times in
Scopus
ETH Bibliography
yes
Altmetrics