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Cited by 24Biochemical and Structural CharacterizationBacteriophages and microbial interactionsBacterial Genetics and Biotechnology

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Atomic structures of a bacteriocin targeting Gram-positive bacteria

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Cai, Xiaoying, He, Yao, Yu, Iris, Imani, Anthony, Scholl, Dean, Miller, Jeff F., Zhou, Z. Hong·2024·Nature Communications
DOI 10.1038/s41467-024-51038-wPMC PMC11329794

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Abstract

Due to envelope differences between Gram-positive and Gram-negative bacteria, engineering precision bactericidal contractile nanomachines requires atomic-level understanding of their structures; however, only those killing Gram-negative bacteria are currently known. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile . Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar linking the sheath with the membrane-penetrating tube. Compared to contractile machines targeting Gram-negative bacteria, major differences reside in the baseplate and contraction magnitude, consistent with target envelope differences. The multifunctional hub-hydrolase protein connects the tube and baseplate and is positioned to degrade peptidoglycan during penetration. The full-length tape measure protein forms a coiled-coil helix bundle homotrimer spanning the entire diffocin. Our study offers mechanical insights and principles for designing potent protein-based precision antibiotics.

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Metadata

Authors
Cai, X., He, Y., Yu, I., Imani, A., Scholl, D., Miller, J. F., & Zhou, Z. H.
Affiliations
California NanoSystems Institute (US)
Corresponding author
  • Miller, Jeff F.
  • Zhou, Z. Hong
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-08-16
Volume
15
Issue
1
Pages
7057-7057
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-51038-w
PMC
PMC11329794
OpenAlex
W4401650850
Cited by
24
References
2
Citations by year
2026: 10 · 2025: 11 · 2024: 3
FWCI
3.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R01GM071940)
  • U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (DE028583)
  • U.S. Department of Health & Human Services | National Institutes of Health (R33AI121692)
  • Kavli Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
bacteriocins, Gram-positive bacteria, Clostridium difficile, atomic structure, base plate, tape measure protein, peptidoglycan degradation

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