PXD058013

PXD058013 is an original dataset announced via ProteomeXchange.

Title	Bidirectional signaling between nucleotide and substrate binding sites in a type IV multidrug ABC transporter
Description	ATP-binding cassette (ABC) transporters use ATP to transport substrates across cellular membranes. In type IV ABC transporters, which includes many multidrug resistance (MDR) pumps, communication between the nucleotide-binding domains (NBDs) and transmembrane domains (TMDs) occurs via intracellular coupling helices. However, the precise mechanism of interdomain crosstalk and coordination between ATP and substrate binding sites remain unclear. Here, we combined NMR spectroscopy, Hydrogen-Deuterium eXchange Mass Spectrometry (HDX-MS), PET-FCS and functional assays to identify a conserved residue cluster at the NBD/TMD interface of the bacterial MDR transporter BmrA. This cluster functions as a bidirectional relay to convey nucleotide and substrate occupancy between the two domains through coupling helix 2. Mutations impact both local and global transporter dynamics. Our findings reveal a novel interdomain communication pathway in type IV ABC transporters, offering insights into the coordination of ligand binding in this important protein family.
HostingRepository	PRIDE
AnnounceDate	2025-11-13
AnnouncementXML	Submission_2025-11-13_04:34:11.722.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julien Marcoux
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	monohydroxylated residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-18 17:13:11	ID requested
⏵ 1	2025-11-13 04:34:19	announced

10.1038/s41467-025-65037-y;

Carrillo VHP, Di Cesare M, Rose-Sperling D, Javed W, Neuweiler H, Marcoux J, Orelle C, Jault JM, Hellmich UA, Bidirectional communication between nucleotide and substrate binding sites in a type IV multidrug ABC transporter. Nat Commun, 16(1):9921(2025) [pubmed]

submitter keyword: BmrA, HDX-MS,LC-MSMS, multidrug transporter

Julien Marcoux
contact affiliation	ProteoToul, 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. PXD058013
     1. Label: PRIDE project
     2. Name: Bidirectional signaling between nucleotide and substrate binding sites in a type IV multidrug ABC transporter