Molecular mechanism of SbmA, a promiscuous transporter exploited by antimicrobial peptides
File(s)
Published version
Author(s)
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.
Date Issued
2021-09-10
Date Acceptance
2021-07-16
Citation
Science Advances, 2021, 7 (37), pp.1-10
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
Japan Society for the Promotion of Science
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.science.org/doi/10.1126/sciadv.abj5363
Grant Number
Japan Society for the Promotion of Science
BB/H01778X/1
Publication Status
Published
Date Publish Online
2021-09-08