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

DOI: 10.1126/sciadv.abj5363 DOI Help

Authors: Dmitry Ghilarov (Jagiellonian University) , Satomi Inaba-Inoue (Imperial College London; Research Complex at Harwell; Japan Synchrotron Radiation Research Institute, SPring-8) , Piotr Stepien (Jagiellonian University) , Feng Qu (Imperial College London; Research Complex at Harwell) , Elizabeth Michalczyk (Jagiellonian University) , Zuzanna Pakosz (Jagiellonian University) , Norimichi Nomura (Kyoto University) , Satoshi Ogasawara (Kyoto University) , Graham Charles Walker (Massachusetts Institute of Technology,) , Sylvie Rebuffat (Muséum National d’Histoire Naturelle, Sorbonne Universités, Centre National de la Recherche Scientifique) , So Iwata (Diamond Light Source) , Jonathan Gardiner Heddle (Jagiellonian University) , Konstantinos Beis (Imperial College London; Research Complex at Harwell)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 7

State: Published (Approved)
Published: September 2021
Diamond Proposal Number(s): 18659

Open Access Open Access

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.

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Other Facilities: SOLARIS

Added On: 18/09/2021 12:43


Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)