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Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides

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Title: Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides
Authors: Ghilarov, D
Inaba-Inoue, S
Stepien, P
Qu, F
Michalczyk, E
Pakosz, Z
Nomura, N
Ogasawara, S
Walker, GC
Rebuffat, S
Iwata, S
Heddle, JG
Beis, K
Item Type: Journal Article
Abstract: Antibiotic metabolites and antimicrobial peptides mediate competition between bacterial species. Many of them hijack inner and outer membrane proteins to enter cells. Sensitivity of enteric bacteria to multiple peptide antibiotics is controlled by the single inner membrane protein SbmA. To establish the molecular mechanism of peptide transport by SbmA and related BacA, we determined their cryo–electron microscopy structures at 3.2 and 6 Å local resolution, respectively. The structures show a previously unknown fold, defining a new class of secondary transporters named SbmA-like peptide transporters. The core domain includes conserved glutamates, which provide a pathway for proton translocation, powering transport. The structures show an outward-open conformation with a large cavity that can accommodate diverse substrates. We propose a molecular mechanism for antibacterial peptide uptake paving the way for creation of narrow-targeted therapeutics.
Issue Date: 10-Sep-2021
Date of Acceptance: 16-Jul-2021
URI: http://hdl.handle.net/10044/1/91606
DOI: 10.1126/sciadv.abj5363
ISSN: 2375-2548
Publisher: American Association for the Advancement of Science
Start Page: 1
End Page: 10
Journal / Book Title: Science Advances
Volume: 7
Issue: 37
Copyright Statement: © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Sponsor/Funder: Japan Society for the Promotion of Science
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: Japan Society for the Promotion of Science
BB/H01778X/1
Publication Status: Published
Online Publication Date: 2021-09-08
Appears in Collections:Faculty of Natural Sciences