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Crystal structure of the anthrax toxin protective antigen
C Petosa1, R J Collier, K R Klimpel
1Biochemistry Department, University of Leicester, UK.
Nature
|February 27, 1997
Summary
The crystal structure of protective antigen (PA) from Bacillus anthracis was determined, revealing its domain organization and heptamer formation mechanism. This structural insight aids understanding of anthrax toxin delivery and potential protein delivery systems.
Area of Science:
- Structural Biology
- Biochemistry
- Microbiology
Background:
- Bacillus anthracis secretes a three-part protein toxin, with protective antigen (PA) as the central component.
- Activated PA forms a heptamer that translocates lethal and edema factors into host cells.
- PA is explored as a general protein delivery system.
Purpose of the Study:
- To determine the crystal structure of monomeric and heptameric protective antigen (PA).
- To elucidate the mechanism of PA heptamerization and membrane insertion.
- To provide insights into PA's role in anthrax pathogenesis and its potential as a delivery vehicle.
Main Methods:
- X-ray crystallography was used to determine the structure of monomeric PA at 2.1 Å and the heptamer at 4.5 Å resolution.
- Analysis of PA domains and their roles in activation, heptamerization, and receptor binding.
- Proposed a model for pH-dependent membrane insertion.
Main Results:
- The crystal structure of monomeric PA revealed four distinct domains.
- Removal of an N-terminal fragment from domain 1 facilitates heptamer assembly.
- The heptamer forms a ring with a negatively charged lumen and exposes a hydrophobic surface for enzyme binding.
Conclusions:
- The study provides high-resolution structural data of protective antigen.
- Structural insights explain PA heptamerization and its role in translocating toxins.
- The findings support the potential of PA as a versatile protein delivery system.