Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin
- University College London, United Kingdom
- Birkbeck College, United Kingdom
- University of Leicester, United Kingdom
- Monash University, Australia
Abstract
Membrane attack complex/perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins constitute a major superfamily of pore-forming proteins that act as bacterial virulence factors and effectors in immune defence. Upon binding to the membrane, they convert from the soluble monomeric form to oligomeric, membrane-inserted pores. Using real-time atomic force microscopy (AFM), electron microscopy (EM) and atomic structure fitting, we have mapped the structure and assembly pathways of a bacterial CDC in unprecedented detail and accuracy, focussing on suilysin from Streptococcus suis. We show that suilysin assembly is a noncooperative process that is terminated before the protein inserts into the membrane. The resulting ring-shaped pores and kinetically trapped arc-shaped assemblies are all seen to perforate the membrane, as also visible by the ejection of its lipids. Membrane insertion requires a concerted conformational change of the monomeric subunits, with a marked expansion in pore diameter due to large changes in subunit structure and packing.
Article and author information
Author details
Reviewing Editor
- Volker Dötsch, Goethe University, Germany
Version history
- Received: August 5, 2014
- Accepted: November 24, 2014
- Accepted Manuscript published: December 2, 2014 (version 1)
- Version of Record published: December 24, 2014 (version 2)
Copyright
© 2014, Leung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin
eLife 3:e04247.
https://doi.org/10.7554/eLife.04247
Further reading
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- Microbiology and Infectious Disease
- Structural Biology and Molecular Biophysics
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