PXD027447

PXD027447 is an original dataset announced via ProteomeXchange.

Title	HDX-MS studies of the bacterial multidrug ABC transporter BmrA in presence or absence of a ligand (rhodamine-6G)
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 R6G molecules bind to the drug-binding cavity at the level of the outer leaflet, between transmembrane (TM) helices 1-2 of one monomer and TM5’-6’ of the other. 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	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:30:59.338.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	2021-07-20 15:21:58	ID requested
1	2022-01-27 05:04:49	announced
2	2023-11-14 08:53:09	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:30:59	announced	2024-10-22: Updated project metadata.

10.1126/SCIADV.ABG9215;

submitter keyword: BmrA, ABC transporter,hydrogen-deuterium MS

Julien Marcoux
contact affiliation	Institute of Pharmacology and Structural Biology (IPBS), CNRS, Toulouse
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. PXD027447
     1. Label: PRIDE project
     2. Name: HDX-MS studies of the bacterial multidrug ABC transporter BmrA in presence or absence of a ligand (rhodamine-6G)