Molecular Playground/ClyA
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IntroductionIntroduction
In progress
About this StructureAbout this Structure
1QOY is a 34 kDa monomer from Escherichia coli (E. coli). It is a pore-forming toxin (PFT) comprised of four alpha helicies, a smaller fifth alpha helix, and a beta tongue. The N-terminus and the C-terminus are highlighted. ClyA has been shown to form pores through a non-classical assembly pathway, excreted in oligomeric form in outer-membrane vesicles (OMV) as pre-pores. Only until ClyA reaches the target host membrane does it form the dodecameric PFT with hemolytic activity, possessing the ability to lyse the host cell.
The protomer of ClyA reveals slight differences between the monomer and protomer (from the dodecameric oligomer). The major conformational changes between the monomer and the protomer are the positions of the N-terminal helix and the beta-tongue. As ClyA oligomerizes and forms a pore, the N-terminal helix swings to the opposite side of the molecule while the beta-tongue changes its conformation and turns into an alpha-helix that interacts with the lipid bilayer.
Its crystal structure, 2WCD, reveals a dodecamer. Larger pores have been isolated, as well. A few research endeavors involving ClyA include using ClyA as part of cancer therapy, as well as a DNA delivery vehicle.
Research on ClyA at UMass AmherstResearch on ClyA at UMass Amherst
The Chen Lab, in collaboration with the Heuck lab, recently published a paper on ClyA assembly. We use a technique commonly used for nanopore sensing called electrophysiology, which allows us to measure the ionic current through the ClyA nanopore.
ReferencesReferences
1. Wallace, a J. et al. E. coli hemolysin E (HlyE, ClyA, SheA): X-ray crystal structure of the toxin and observation of membrane pores by electron microscopy. Cell 100, 265–76 (2000).
2. Atkins, a et al. Structure-function relationships of a novel bacterial toxin, hemolysin E. The role of alpha G. J. Biol. Chem. 275, 41150–5 (2000).
3. Mueller, M., Grauschopf, U., Maier, T., Glockshuber, R. & Ban, N. The structure of a cytolytic alpha-helical toxin pore reveals its assembly mechanism. Nature 459, 726–30 (2009).
4. Fahie, M. et al. A non-classical assembly pathway of Escherichia coli pore-forming toxin cytolysin A. J. Biol. Chem. 288, 31042–51 (2013).