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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
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, 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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