Shared structural mechanisms of alternating access between the secondary peptide transporter SbmA and ABC transporters.
Peptide transporters are finally getting the structural attention they deserve. Researchers just cracked open the details of SbmA, a membrane transporter in E. coli famous for importing antimicrobial peptides. The big reveal: SbmA doesn’t just look like the more famous ATP-binding cassette (ABC) transporters—it actually works in similar ways, even though it uses a totally different energy source.
Nat Commun
by Ettema TW, Inaba-Inoue S, Thangaratnarajah C et al.
“Shared structural mechanisms of alternating access between the secondary peptide transporter SbmA and ABC transporters. Ettema TW(#)(1), Inaba-Inoue S(#)(2)(3)(4), Thangaratnarajah C(#)(1)(5), Alves da Silva L(6), Senning N(6), Clarke A(6), Stepien P(7)(8), Shah A(9)(10), Ma Y(9)(10), Hardman K(11), David S(12), El Mkami H(13), Heddle JG(7)(8), Nomura N(14), Ogasawara S(14), Iwata S(14), Ghilarov D(15)(16), Pliotas C(17)(18), Stockner T(19), Slotboom DJ(20), Beis K(21)(22). Author information: (1)Membrane Enzymology Group, Groningen, Biomolecular Sciences and Biotechnology, Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands. (2)Department of Life Sciences, Imperial College London, London, UK. (3)Rutherford Appleton Laboratory, Research Complex at Harwell, Oxfordshire, UK. (4)Structural Biology Research Center, Institute of Materials Structure, Science, High Energy Accelerator Research Organization, Tsukuba, Japan. (5)Steinmetz Building, Granta Park, Nxera Pharma, Cambridge, UK. (6)Institute of Pharmacology, Medical University of Vienna, Vienna, Austria. (7)Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. (8)Centre for Programmable Biological Matter, Durham University, Durham, UK. (9)BioEmPiRe Centre for Structural Biological EPR Spectroscopy, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. (10)Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. (11)Astbury Centre for Structural Molecular Biology, School of Biomedical Sciences, University of Leeds, Leeds, UK. (12)Centre for Genomic Pathogen Surveillance, Pandemic Sciences Institute, University of Oxford, Oxford, UK. (13)School of Physics and Astronomy, University of St. Andrews, St. Andrews, UK. (14)Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. (15)Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. dmitry.ghilarov@bioch.ox.ac.uk. (16)Department of Biochemistry, University of Oxford, Oxford, UK. dmitry.ghilarov@bioch.ox.ac.uk. (17)BioEmPiRe Centre for Structural Biological EPR Spectroscopy, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. christos.pliotas@manchester.ac.uk. (18)Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. christos.pliotas@manchester.ac.uk. (19)Institute of Pharmacology, Medical University of Vienna, Vienna, Austria. thomas.stockner@meduniwien.ac.at. (20)Membrane Enzymology Group, Groningen, Biomolecular Sciences and Biotechnology, Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands. d.j.slotboom@rug.nl. (21)Department of Life Sciences, Imperial College London, London, UK. kbeis@imperial.ac.uk. (22)Rutherford Appleton Laboratory, Research Complex at Harwell, Oxfordshire, UK. kbeis@imperial.ac.uk. (#)Contributed equally 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 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 transporters, 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. © 2026. The Author(s). Conflict of interest statement: Competing interests: The authors declare no competing interests.”
SbmA belongs to the SLiPT family, running on the proton gradient, not ATP. For years, nobody knew if its mechanism matched ABC transporters or if similarities were just skin-deep. The new study used cryo-EM to capture SbmA in both occluded and inward-facing states. These snapshots look almost identical to the alternate conformations seen in ABC transporters. Key takeaway: the blueprint for moving peptides across the membrane seems more universal than anyone thought.
Here’s the twist: while ABC transporters flip between states using ATP, SbmA’s shape-shifting is triggered by pH changes. The team combined electron paramagnetic resonance (EPR) and molecular dynamics simulations to show that protons do the job of ATP here, controlling access and internalization of peptides.
Why does this matter? If you’re studying how bacteria move peptides or designing new research compounds, these insights streamline your understanding. Now, you don’t have to reinvent the wheel for every transporter—there’s a shared playbook. That opens the door to better engineering of transporter systems and smarter peptide delivery strategies.
For researchers looking to dig deeper or source compounds for related experiments, check out the peptide research index and our vendor directory.
Bottom line: SbmA bridges the gap between two transporter worlds, and the rules of the game are more similar than they look.
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