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PXD022185

PXD022185 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOutward-facing structures of a multidrug ABC exporter with and without bound drug
DescriptionMultidrug 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.
HostingRepositoryPRIDE
AnnounceDate2021-03-25
AnnouncementXMLSubmission_2021-03-25_07:25:09.293.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJulien Marcoux
SpeciesList scientific name: Bacillus subtilis; NCBI TaxID: 1423;
ModificationListmonohydroxylated residue
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-26 05:12:45ID requested
12021-03-25 07:25:09announced
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 affiliationProteomics and Mass Spectrometry of Biomolecules, Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
contact emailjulien.marcoux@ipbs.fr
lab head
Julien Marcoux
contact affiliationIPBS
contact emailjulien.marcoux@ipbs.fr
dataset submitter
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Dataset FTP location
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