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Discovery and structural characterization of the D-box, a conserved TonB motif that couples an inner-membrane motor to outer-membrane transport
Journal article   Open access   Peer reviewed

Discovery and structural characterization of the D-box, a conserved TonB motif that couples an inner-membrane motor to outer-membrane transport

Patrick J. Loll, Kimberly C. Grasty, David D. Shultis, Nicholas J. Guzman and Michael C. Wiener
The Journal of biological chemistry, 105723
02 Feb 2024
DOI: https://doi.org/10.1016/j.jbc.2024.105723
PMID: 38311172
url
https://doi.org/10.1016/j.jbc.2024.105723View
Published, Version of Record (VoR) Open

Abstract

Antibiotic resistance ExbBD Gram-negative bacteria membrane transport outer membrane plasma membrane proton motive force siderophore TonB TonB-dependent transport
Gram-negative bacteria use TonB-dependent transport to take up nutrients from the external environment, employing the Ton complex to import a variety of nutrients that are either scarce or too large to cross the outer membrane unaided. The Ton complex contains an inner-membrane motor (ExbBD) that generates force, as well as nutrient-specific transport proteins on the outer membrane. These two components are coupled by TonB, which transmits the force from the inner to the outer membrane. TonB contains an N-terminus anchored in the inner membrane, a C-terminal domain that binds the outer-membrane transporter, and a proline-rich linker connecting the two. While much is known about the interaction between TonB and outer-membrane transporters, the critical interface between TonB and ExbBD is less well understood. Here, we identify a conserved motif within TonB that we term the D-box, which serves as an attachment point for ExbD. We characterize the interaction between ExbD and the D-box both functionally and structurally, showing that a homodimer of ExbD captures one copy of the D-box peptide via beta-strand recruitment. We additionally show that both the D-box motif and ExbD are conserved in a range of Gram-negative bacteria, including members of the ESKAPE group of pathogens. The ExbD:D-box interaction is likely to represent an important aspect of force transduction between the inner and outer membranes. Given that TonB-dependent transport is an important contributor to virulence, this interaction is an intriguing potential target for novel antibacterial therapies.

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