Atomic structures of a bacteriocin targeting Gram-positive bacteria.

Bacteriocins / chemistry Clostridioides difficile / drug effects Anti-Bacterial Agents / pharmacology Bacterial Proteins / metabolism Models, Molecular Gram-Positive Bacteria / drug effects Peptidoglycan / metabolism Crystallography, X-Ray

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
16 Aug 2024
Historique:
received: 19 03 2024
accepted: 29 07 2024
medline: 17 8 2024
pubmed: 17 8 2024
entrez: 16 8 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-51038-w PMID: 39152109
pubmed: 39152109
doi: 10.1038/s41467-024-51038-w
pii: 10.1038/s41467-024-51038-w
doi:

Substances chimiques

Bacteriocins 0
Anti-Bacterial Agents 0
Bacterial Proteins 0
Peptidoglycan 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7057

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R01GM071940
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)
ID : DE028583
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R33AI121692

Informations de copyright

© 2024. The Author(s).

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Auteurs

Xiaoying Cai (X)

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
ORCID: 0000-0001-6694-2154

Yao He (Y)

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
ORCID: 0000-0002-1368-6422

Iris Yu (I)

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, USA.

Anthony Imani (A)

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, USA.

Dean Scholl (D)

Pylum Biosciences, San Francisco, CA, 94080, USA.

Jeff F Miller (JF)

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. jfmiller@ucla.edu.
The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, USA. jfmiller@ucla.edu.

Z Hong Zhou (ZH)

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Hong.Zhou@UCLA.edu.
The California NanoSystems Institute (CNSI), University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Hong.Zhou@UCLA.edu.
ORCID: 0000-0002-8373-4717

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Perforines › Bactériocines › Atomic structures of a bacteriocin targeting...
questionsmedicales.fr › Bactéries › Firmicutes › Clostridiales › Clostridioides › Clostridium difficile › Atomic structures of a bacteriocin targeting...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › Atomic structures of a bacteriocin targeting...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines bactériennes › Atomic structures of a bacteriocin targeting...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Atomic structures of a bacteriocin targeting...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Atomic structures of a bacteriocin targeting...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes bactériens › Polyosides bactériens › Peptidoglycane › Atomic structures of a bacteriocin targeting...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Cristallographie aux rayons X › Atomic structures of a bacteriocin targeting...