Shared structural mechanisms of alternating access between the secondary peptide transporter SbmA and ABC transporters
File(s)
Published version
Author(s)
Ettema, Thijs W
Inaba-Inoue, Satomi
Thangaratnarajah, Chancievan
da Silva, Leticia Alves
Senning, Nikas
Type
Journal Article
Abstract
SbmA is a membrane transporter from Escherichia coli that imports antimicrobial peptides. SbmA belongs to the SbmA-like peptide transporter (SLiPT) family. Although the protein is a secondary active transporter that is energized by the proton gradient, it is structurally related to the transmembrane domain (TMD) of ATP-binding cassette (ABC) transporters. SbmA therefore bridges the structural divide between primary and 61
secondary transporters. However, it remains unclear, if SbmA also shares the mechanism of alternating access with ABC transporters, because only a single (outward-open) state is resolved. Here, we show by sequence analysis that SbmA is likely evolved from the TMD of an early ancestor of the ABC transporter YddA. We determine the cryogenic electron microscopy structures of SbmA in occluded and inward-facing states. These conformations closely resemble equivalent states found in ABC trans-
porters, indicating a shared structural mechanism of transport. In contrast to ABC transporters, where nucleotide binding, hydrolysis and release steer conformational changes necessary for substrate translocation, electron paramagnetic resonance
(EPR) spectroscopy and molecular dynamics (MD) simulations reveal how pH changes induce conformational transitions in SbmA, consistent with a mechanism of substrate internalization that utilizes the transmembrane proton gradient.
secondary transporters. However, it remains unclear, if SbmA also shares the mechanism of alternating access with ABC transporters, because only a single (outward-open) state is resolved. Here, we show by sequence analysis that SbmA is likely evolved from the TMD of an early ancestor of the ABC transporter YddA. We determine the cryogenic electron microscopy structures of SbmA in occluded and inward-facing states. These conformations closely resemble equivalent states found in ABC trans-
porters, indicating a shared structural mechanism of transport. In contrast to ABC transporters, where nucleotide binding, hydrolysis and release steer conformational changes necessary for substrate translocation, electron paramagnetic resonance
(EPR) spectroscopy and molecular dynamics (MD) simulations reveal how pH changes induce conformational transitions in SbmA, consistent with a mechanism of substrate internalization that utilizes the transmembrane proton gradient.
Date Issued
2026-06-29
Date Acceptance
2026-03-21
Citation
Nature Communications, 2026, 17 (1)
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
17
Issue
1
Copyright Statement
©The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view acopyofthislicence, visit http://creativecommons.org/ licenses/by/4.0/.
License URL
Identifier
10.1038/s41467-026-71633-3
Publication Status
Published
Article Number
5619
Date Publish Online
2026-04-15