Conformational cycle of a protease-containing ABC transporter in lipid nanodiscs reveals the mechanism of cargo-protein coupling

Ruojing Zhang, Kevin L. Jagessar, Matthew Brownd, Adithya Polasa, Richard A. Stein, Mahmoud Moradi, Erkan Karakas and Hassane S. Mchaourab ()
Additional contact information
Ruojing Zhang: Vanderbilt University
Kevin L. Jagessar: Vanderbilt University
Matthew Brownd: University of Arkansas
Adithya Polasa: University of Arkansas
Richard A. Stein: Vanderbilt University
Mahmoud Moradi: University of Arkansas
Erkan Karakas: Vanderbilt University
Hassane S. Mchaourab: Vanderbilt University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Protease-containing ABC transporters (PCATs) couple the energy of ATP hydrolysis to the processing and export of diverse cargo proteins across cell membranes to mediate antimicrobial resistance and quorum sensing. Here, we combine biochemical analysis, single particle cryoEM, and DEER spectroscopy in lipid bilayers along with computational analysis to illuminate the structural and energetic underpinnings of coupled cargo protein export. Our integrated investigation uncovers competitive interplay between nucleotides and cargo protein binding that ensures the latter’s orderly processing and subsequent transport. The energetics of cryoEM structures in lipid bilayers are congruent with the inferred mechanism from ATP turnover analysis and reveal a snapshot of a high-energy outward-facing conformation that provides an exit pathway into the lipid bilayer and/or the extracellular side. DEER investigation of the core ABC transporter suggests evolutionary tuning of the energetic landscape to fulfill the function of substrate processing prior to export.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53420-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53420-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53420-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().