Flexible-to-rigid transition is central for substrate transport in the ABC transporter BmrA from Bacillus subtilis
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
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
Journal / seriesCommunications Biology
Pages / Article No.
PublisherNature Publishing Group
Organisational unit03496 - Meier, Beat H. / Meier, Beat H.
159707 - NMR studies in the Solid State (SNF)
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