Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/31848
Title: Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin
Authors: Leung, C.
Dudkina, N. V.
Lukoyanova, N.
Hodel, A. W.
Farabella, I.
Pandurangan, A. P.
Jahan, Nasrin
Damaso, Mafalda Pires
Osmanovic, D.
Reboul, C. F.
Dunstone, M. A.
Andrew, Peter W.
Lonnen, Rana
Topf, M.
Saibil, H. R.
Hoogenboom, B. W.
First Published: 2-Dec-2014
Publisher: 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.
DOI Link: 10.7554/eLife.04247.001
ISSN: 2050-084X
eISSN: 2050-084X
Links: http://elifesciences.org/content/3/e04247/abstract-1
http://hdl.handle.net/2381/31848
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright 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: Figure supplement 1. Symmetry of suilysin prepores and pores, determined by negative-stain EM. DOI: 10.7554/eLife.04247.004 Figure supplement 2. Resolution curves for EM maps. DOI: 10.7554/eLife.04247.005 Figure supplement 3. Electrostatic potential maps and interacting residues. DOI: 10.7554/eLife.04247.006 Figure supplement 4. Comparison between prepore and crystal structure conformations. DOI: 10.7554/eLife.04247.007 Accession codes for EM maps: prepore EMD-12698, pore EMD-12711.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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