The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device
The crystal structure of the complex formed by the B and C toxin complex proteins is reported, revealing how toxin complexes are processed and protected; the proteins assemble to form a large hollow structure that sequesters the cytotoxic portion of the C protein, and a β-propeller domain mediates a...
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Veröffentlicht in: | Nature (London) 2013-09, Vol.501 (7468), p.547-550 |
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Zusammenfassung: | The crystal structure of the complex formed by the B and C toxin complex proteins is reported, revealing how toxin complexes are processed and protected; the proteins assemble to form a large hollow structure that sequesters the cytotoxic portion of the C protein, and a β-propeller domain mediates attachment to the A protein in the native ABC complex.
The BC of ABC toxins
Shaun Lott and colleagues have determined the crystal structure of the complex formed by the B and C proteins of the ABC toxin from the insect pathogen
Yersinia entomophaga
. Toxin complexes have previously been visualized by single-particle electron microscopy, but no high-resolution structures for the component proteins have been available. The new data reveal a large hollow structure that encapsulates and sequesters the cytotoxic portion of the C protein and a β-propeller domain that mediates attachment to the A protein in the native ABC complex. This is the first demonstration of a mechanism for toxin delivery, complementing the recently published cryo-electron microscopy structure of an A component.
The ABC toxin complexes produced by certain bacteria are of interest owing to their potent insecticidal activity
1
,
2
and potential role in human disease
3
. These complexes comprise at least three proteins (A, B and C), which must assemble to be fully toxic
4
. The carboxy-terminal region of the C protein is the main cytotoxic component
5
, 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
5
. Toxin complexes have been visualized using single-particle electron microscopy
6
,
7
, 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 nati |
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ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/nature12465 |