Structure of anthrax lethal toxin prepore complex suggests a pathway for efficient cell entry
Abstract
Anthrax toxin comprises three soluble proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA must be cleaved by host proteases before it oligomerizes and forms a prepore, to which LF and EF bind. After endocytosis of this tripartite complex, the prepore transforms into a narrow transmembrane pore that delivers unfolded LF and EF into the host cytosol. Here, we find that translocation of multiple 90-kD LF molecules is rapid and efficient. To probe the molecular basis of this translocation, we calculated a three-dimensional map of the fully loaded (PA63)7–(LF)3 prepore complex by cryo–electron microscopy (cryo-EM). The map shows three LFs bound in a similar way to one another, via their N-terminal domains, to the surface of the PA heptamer. The model also reveals contacts between the N- and C-terminal domains of adjacent LF molecules. We propose that this molecular arrangement plays an important role in the maintenance of translocation efficiency through the narrow PA pore.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 26, 2016
- Source ID
- 10.1085/jgp.201611617
Entities
People
- Annemarie Donoghue
- Aviroop Biswas
- Dorit Hanein
- Driss Mountassif
- Eugenio Santelli
- Isabelle Rouiller
- Lucien Fabre
- Niels Volkmann
- Rikard Blunck
- Robert Liddington
Organizations
- Canada Foundation for Innovation
- Canadian Institutes of Health Research
- McGill University
- National Institutes of Health
- Natural Sciences and Engineering Research Council
- Sanford Burnham Prebys Medical Discovery Institute
- United States Department of Defense
- Université de Montréal