Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems

Robert P. Morse; Kiel C. Nikolakakis; Julia L.E. Willett; Elias Gerrick; David A. Low; Christopher S. Hayes; Celia W. Goulding

doi:10.1073/pnas.1216238110

Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems

Robert P. Morse, Kiel C. Nikolakakis, Julia L.E. Willett, Elias Gerrick, David A. Low, Christopher S. Hayes, Celia W. Goulding

Research output: Contribution to journal › Article › peer-review

86 Scopus citations

Abstract

Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins thatmediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn²⁺-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual β-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.

Original language	English (US)
Pages (from-to)	21480-21485
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	109
Issue number	52
DOIs	https://doi.org/10.1073/pnas.1216238110
State	Published - Dec 26 2012
Externally published	Yes

Keywords

Bacterial competition
Structural biology
tRNase activity
β-complementation

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10.1073/pnas.1216238110

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abstract = "Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins thatmediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn2+-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual β-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.",

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AU - Morse, Robert P.

AU - Nikolakakis, Kiel C.

AU - Willett, Julia L.E.

AU - Gerrick, Elias

AU - Low, David A.

AU - Hayes, Christopher S.

AU - Goulding, Celia W.

PY - 2012/12/26

Y1 - 2012/12/26

N2 - Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins thatmediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn2+-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual β-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.

AB - Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins thatmediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn2+-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual β-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.

KW - Bacterial competition

KW - Structural biology

KW - tRNase activity

KW - β-complementation

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Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems

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