Probing the Allosteric NBD-TMD Crosstalk in the ABC Transporter MsbA by Solid-state NMR

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Jan 5

PMID 38182790

Authors

S Y Phoebe Novischi

Andrea Karoly-Lakatos

Kerby Chok

Christian Bonifer

Johanna Becker-Baldus

Clemens Glaubitz

Affiliations

Soon will be listed here.

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.

Citing Articles

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