Probing the allosteric NBD-TMD crosstalk in the ABC transporter MsbA by solid-state NMR.
Commun Biol
; 7(1): 43, 2024 01 05.
Article
em En
| MEDLINE
| ID: mdl-38182790
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.
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Base de dados:
MEDLINE
Assunto principal:
Imageamento por Ressonância Magnética
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Transportadores de Cassetes de Ligação de ATP
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article