PXD028663

PXD028663 is an original dataset announced via ProteomeXchange.

Title	Structural insights into the catalytic cycle of a bacterial multidrug ABC efflux pump
Description	ABC (“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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:35:36.862.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

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-20 23:03:22	ID requested
1	2022-03-24 05:13:00	announced
⏵ 2	2024-10-22 05:35:37	announced	2024-10-22: Updated project metadata.

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;

submitter keyword: Multidrug resistance,hydrogen-deuterium exchange MS, ABC transporter, BmrA

Julien Marcoux
contact affiliation	Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France
contact email	julien.marcoux@ipbs.fr
lab head
Julien Marcoux
contact affiliation	IPBS
contact email	julien.marcoux@ipbs.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028663
     1. Label: PRIDE project
     2. Name: Structural insights into the catalytic cycle of a bacterial multidrug ABC efflux pump