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|Title:||Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin|
Dudkina, N. V.
Hodel, A. W.
Pandurangan, A. P.
Pires Damaso, M.
Osmanović, D. J.
Reboul, C. F.
Dunstone, M. A.
Andrew, Peter William
Saibil, H. R.
Hoogenboom, B. W.
|Publisher:||eLife Sciences Publications|
|Citation:||Elife, 2014, 3, e04247|
|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.|
|Rights:||Copyright © 2014, Leung et al This article is distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use and redistribution provided that the original author and source are credited.|
|Description:||This publication has a correction, available at http://dx.doi.org/10.7554/eLife.06740|
|Appears in Collections:||Published Articles, Dept. of Infection, Immunity and Inflammation|
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