Projects per year
Abstract
The cholesterol-dependent cytolysin perfringolysin O (PFO) is secreted by Clostridium perfringens as a bacterial virulence factor able to form giant ring-shaped pores that perforate and ultimately lyse mammalian cell membranes. To resolve the kinetics of all steps in the assembly pathway, we have used single-molecule fluorescence imaging to follow the dynamics of PFO on dye- loaded liposomes that lead to opening of a pore and release of the encapsulated dye. Formation of a long-lived membrane-bound PFO dimer nucleates the growth of an irreversible oligomer. The growing oligomer can insert into the membrane and open a pore at stoichiometries ranging from tetramers to full rings (~35 mers), whereby the rate of insertion increases linearly with the number of subunits. Oligomers that insert before the ring is complete continue to grow by monomer addi¬tion post insertion. Overall, our observations suggest that PFO membrane insertion is kinetically controlled.
Original language | English |
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Article number | e74901 |
Number of pages | 34 |
Journal | eLife |
Volume | 11 |
DOIs | |
Publication status | Published - 2022 |
Projects
- 2 Finished
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The HIV capsid is a functional scaffold that directs bidirectional cargo transport
Boecking, T., Jacques, D. A., Arumugam, S., Stear, J. & McKenney, R.
1/01/20 → 31/12/22
Project: Research
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Understanding pore formation by the complement Membrane Attack Complex
Australian Research Council (ARC), Monash University
30/06/16 → 31/12/21
Project: Research