Document Type
Article
Publication Date
10-20-2024
Keywords
PCATs, lipids, cargo proteins
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.
Citation
Zhang, R., Jagessar, K.L., Brownd, M. et al. Conformational cycle of a protease-containing ABC transporter in lipid nanodiscs reveals the mechanism of cargo-protein coupling. Nat Commun 15, 9055 (2024). https://doi.org/10.1038/s41467-024-53420-0
Supplementary Information
41467_2024_53420_MOESM2_ESM.pdf (1566 kB)
Reporting Summary
41467_2024_53420_MOESM3_ESM.pdf (815 kB)
Transparent Peer Review File
41467_2024_53420_MOESM4_ESM.xlsx (50 kB)
Source data
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
