The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device

Busby, Jason N., Panjikar, Santosh, Landsberg, Michael J., Hurst, Mark R. H. and Lott, J. Shaun (2013) The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device. Nature, 501 7468: 547-550. doi:10.1038/nature12465

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Author Busby, Jason N.
Panjikar, Santosh
Landsberg, Michael J.
Hurst, Mark R. H.
Lott, J. Shaun
Title The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2013-09-01
Year available 2013
Sub-type Article (original research)
DOI 10.1038/nature12465
Open Access Status File (Author Post-print)
Volume 501
Issue 7468
Start page 547
End page 550
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
The ABC toxin complexes produced by certain bacteria are of interest owing to their potent insecticidal activity and potential role in human disease. These complexes comprise at least three proteins (A, B and C), which must assemble to be fully toxic. The carboxy-terminal region of the C protein is the main cytotoxic component, and is poorly conserved between different toxin complexes. A general model of action has been proposed, in which the toxin complex binds to the cell surface via the A protein, is endocytosed, and subsequently forms a pH-triggered channel, allowing the translocation of C into the cytoplasm, where it can cause cytoskeletal disruption in both insect and mammalian cells. Toxin complexes have been visualized using single-particle electron microscopy, but no high-resolution structures of the components are available, and the role of the B protein in the mechanism of toxicity remains unknown. Here we report the three-dimensional structure of the complex formed between the B and C proteins, determined to 2.5 Å by X-ray crystallography. These proteins assemble to form an unprecedented, large hollow structure that encapsulates and sequesters the cytotoxic, C-terminal region of the C protein like the shell of an egg. The shell is decorated on one end by a β-propeller domain, which mediates attachment of the B-C heterodimer to the A protein in the native complex. The structure reveals how C auto-proteolyses when folded in complex with B. The C protein is the first example, to our knowledge, of a structure that contains rearrangement hotspot (RHS) repeats, and illustrates a marked structural architecture that is probably conserved across both this widely distributed bacterial protein family and the related eukaryotic tyrosine-aspartate (YD)-repeat-containing protein family, which includes the teneurins. The structure provides the first clues about the function of these protein repeat families, and suggests a generic mechanism for protein encapsulation and delivery.
Keyword Photorhabdus Luminescens Toxins
Escherichia coli
Biological Macromolecules
Insecticidal Activity
Solution Scattering
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 31 times in Scopus Article | Citations
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