1. Academic Validation
  2. Probing the allosteric NBD-TMD crosstalk in the ABC transporter MsbA by solid-state NMR

Probing the allosteric NBD-TMD crosstalk in the ABC transporter MsbA by solid-state NMR

  • Commun Biol. 2024 Jan 5;7(1):43. doi: 10.1038/s42003-023-05617-0.
S Y Phoebe Novischi 1 Andrea Karoly-Lakatos 1 Kerby Chok 1 Christian Bonifer 1 Johanna Becker-Baldus 1 Clemens Glaubitz 2
Affiliations

Affiliations

  • 1 Institute for Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt, Max von Laue Str. 9, 60438, Frankfurt, Germany.
  • 2 Institute for Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt, Max von Laue Str. 9, 60438, Frankfurt, Germany. glaubitz@em.uni-frankfurt.de.
Abstract

The ABC transporter MsbA plays a critical role in Gram-negative bacteria in the regulation of the outer membrane by translocating core-LPS across the inner membrane. Additionally, a broad substrate specificity for lipophilic drugs has been shown. The allosteric interplay between substrate binding in the transmembrane domains and ATP binding and turnover in the nucleotide-binding domains must be mediated via the NBD/TMD interface. Previous studies suggested the involvement of two intracellular loops called coupling helix 1 and 2 (CH1, CH2). Here, we demonstrate by solid-state NMR spectroscopy that substantial chemical shift changes within both CH1 and CH2 occur upon substrate binding, in the ATP hydrolysis transition state, and upon inhibitor binding. CH2 is domain-swapped within the MsbA structure, and it is noteworthy that substrate binding induces a larger response in CH2 compared to CH1. Our data demonstrate that CH1 and CH2 undergo structural changes as part of the TMD-NBD cross-talk.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-125176
    98.14%, MsbA Antagonist