Leung, C. and Dudkina, N.V. and Lukoyanova, Natalya and Hodel, A.W. and Farabella, I. and Pandurangan, A.P. and Jahan, N. and Pires Damaso, M. and Osmanović, D. and Reboul, C.F. and Dunstone, M.A. and Andrew, P.W. and Lonnen, R. and Topf, Maya and Saibil, Helen R. and Hoogenboom, B.W. (2014) Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin. eLife 3 , ISSN 2050-084X.
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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.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | Research article, Biophysics and structural biology, bacterial toxins, cholesterol-dependent cytolysins, membrane pore formation, pore-forming proteins, S. suis |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Bioinformatics, Bloomsbury Centre for (Closed), Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 05 Dec 2014 10:17 |
| Last Modified: | 02 Aug 2023 17:14 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/11225 |
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