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TitleThe unique architecture of umbrella toxins permits a two-tiered molecular bet-hedging strategy for interbacterial antagonism.
Journal, issue, pagesCell, Vol. 189, Issue 2, Page 495-510.e20, Year 2026
Publish dateDec 2, 2025
AuthorsQinqin Zhao / Jiri Vlach / Young-Jun Park / Yongjun Tan / Savannah K Bertolli / Pooja Srinivas / Pinyu Liao / Connor R Fitzpatrick / Jeffery L Dangl / Parastoo Azadi / Frank DiMaio / S Brook Peterson / Dapeng Zhang / David Veesler / Joseph D Mougous /
PubMed AbstractBacteria exist in competitive and rapidly changing environments in which the nature of future threats cannot be easily predicted. Streptomyces coelicolor produces three antibacterial umbrella ...Bacteria exist in competitive and rapidly changing environments in which the nature of future threats cannot be easily predicted. Streptomyces coelicolor produces three antibacterial umbrella particles that harbor distinct polymorphic toxin domains and an overlapping set of six diversified lectins. Here, we show that the exquisite specificity of umbrella particles derives from lectin-mediated species-specific binding to previously undescribed hypervariable surface glycoconjugates. A cryo-electron microscopy (cryo-EM) structure of one such lectin in complex with its oligosaccharide substrate defines the molecular basis for targeting through the coordinated recognition of multiple glycan features. Biochemical and genetic studies of several target species, in conjunction with lectin-swapping experiments, support a model whereby S. coelicolor umbrella toxin diversification at the levels of lectin composition and toxin polymorphism represents a unique, two-tiered bet-hedging strategy. Bioinformatic analyses support this as a means by which the unusual architecture of umbrella toxins offers Streptomyces a generalizable strategy to antagonize an unpredictable array of competitors.
External linksCell / PubMed:41338195
MethodsEM (helical sym.) / EM (single particle)
Resolution3.4 - 4.3 Å
Structure data

70396

9oee

EMDB-70396, PDB-9oee:
S. griseus TUA bound UmbA4 complexes
Method: EM (helical sym.) / Resolution: 3.4 Å

EMDB-73973: Streptomyces coelicolor UmbA4 complex
Method: EM (single particle) / Resolution: 4.3 Å

Chemicals

ChemComp-A2G:
2-acetamido-2-deoxy-alpha-D-galactopyranose

PDB-1cay:
WILD-TYPE AND E106Q MUTANT CARBONIC ANHYDRASE COMPLEXED WITH ACETATE

PDB-1caz:
WILD-TYPE AND E106Q MUTANT CARBONIC ANHYDRASE COMPLEXED WITH ACETATE

Source
  • streptomyces coelicolor (bacteria)
KeywordsTOXIN / Teichuronic acid / UmbA4 / Umbrella toxin / Seattle structural genomics center for infectious disease / SSGCID

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