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PXD028663

PXD028663 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural insights into the catalytic cycle of a bacterial multidrug ABC efflux pump
DescriptionABC (“ATP-Binding Cassette”) exporters of the type IV subfamily gather transporters involved in the efflux of many compounds and notably those capable to confer multidrug resistance like the mammalian P-glycoprotein or the bacterial transporter BmrA. They function according to an alternating access mechanism between inward-facing (IF) and outward-facing (OF) conformations, but the extent of physical separation between the two nucleotide-binding domains (NBDs) in different states is still unsettled. Small Angle Neutron Scattering (SANS) and hydrogen/deuterium exchange coupled to mass spectrometry (HDX-MS) were used to highlight different conformational states of BmrA during its catalytic cycle. In particular, mutation of the invariant Lysine residue of the Walker-A motif (K380A) captures BmrA in an ATP-bound IF conformation prior to NBD closure. While in the transition-like state induced by vanadate, wild-type BmrA is mainly in an OF conformation, it and populates only IF conformations only in the presence of ADP/Mg. Importantly, in this post-hydrolytic step, distances between the two NBDs of BmrA appears to be more separated than in the apo state, but they remains shorter than in the widest opening found in the related MsbA transporter. Overall, our results highlight the main steps of the catalytic cycle of a homodimeric bacterial multidrug transporter and underline structural and functional commonalities as well as oddities among the type IV subfamily of ABC exporters.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:35:36.862.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
02021-09-20 23:03:22ID requested
12022-03-24 05:13:00announced
22024-10-22 05:35:37announced2024-10-22: Updated project metadata.
Publication List
Javed W, Vallet S, Clement MP, Le Roy A, Moulin M, H, ä, rtlein M, Breyton C, Burlet-Schiltz O, Marcoux J, Orelle C, Ebel C, Martel A, Jault JM, Structural Insights into the Catalytic Cycle of a Bacterial Multidrug ABC Efflux Pump. J Mol Biol, 434(9):167541(2022) [pubmed]
10.1016/j.jmb.2022.167541;
Keyword List
submitter keyword: Multidrug resistance,hydrogen-deuterium exchange MS, ABC transporter, BmrA
Contact List
Julien Marcoux
contact affiliationInstitut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, 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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