PXD022185 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Outward-facing structures of a multidrug ABC exporter with and without bound drug |
Description | Multidrug ATP-Binding Cassette (ABC) exporters use an alternating access mechanism to translocate drugs across membranes, but the molecular mechanism of substrate release is still elusive due to the poor affinity of the drug-binding pocket for its ligand at this stage. Here, we bring new information on this mechanism by resolving two ATP-bound outward-facing conformations of the homodimer BmrA from Bacillus subtilis by X-ray crystallography with no drug bound and by cryo-EM in the presence of rhodamine 6G. This revealed the first structure of a multidrug pump with a substrate bound to the drug-binding pocket in a pre-release state. Two molecules of the dye are located in an hydrophobic region at the level of the outer leaflet between transmembrane (TM) helices 1, 2 and 6. Markedly, the X-ray structures display a half-closed TM1-2 region that is widely open in the cryo-EM one. Hydrogen-Deuterium exchange coupled to mass spectrometry (HDX-MS) and molecular dynamics simulations confirmed the high flexibility of this region, presumably driving the release of structurally divergent compounds. |
HostingRepository | PRIDE |
AnnounceDate | 2021-03-25 |
AnnouncementXML | Submission_2021-03-25_07:25:09.293.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Julien Marcoux |
SpeciesList | scientific name: Bacillus subtilis; NCBI TaxID: 1423; |
ModificationList | monohydroxylated residue |
Instrument | Synapt MS |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-26 05:12:45 | ID requested | |
⏵ 1 | 2021-03-25 07:25:09 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: membrane exporter crystal and cryo-EM structure, substrate release, transport mechanism, hydrogen-deuterium exchange, nanodiscs |
Contact List
Julien Marcoux |
contact affiliation | Proteomics and Mass Spectrometry of Biomolecules, Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France |
contact email | julien.marcoux@ipbs.fr |
lab head | |
Julien Marcoux |
contact affiliation | IPBS |
contact email | julien.marcoux@ipbs.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022185
- Label: PRIDE project
- Name: Outward-facing structures of a multidrug ABC exporter with and without bound drug