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Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin
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 oligome...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381977/ https://www.ncbi.nlm.nih.gov/pubmed/25457051 http://dx.doi.org/10.7554/eLife.04247 |
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author | Leung, Carl Dudkina, Natalya V Lukoyanova, Natalya Hodel, Adrian W Farabella, Irene Pandurangan, Arun P Jahan, Nasrin Pires Damaso, Mafalda Osmanović, Dino Reboul, Cyril F Dunstone, Michelle A Andrew, Peter W Lonnen, Rana Topf, Maya Saibil, Helen R Hoogenboom, Bart W |
author_facet | Leung, Carl Dudkina, Natalya V Lukoyanova, Natalya Hodel, Adrian W Farabella, Irene Pandurangan, Arun P Jahan, Nasrin Pires Damaso, Mafalda Osmanović, Dino Reboul, Cyril F Dunstone, Michelle A Andrew, Peter W Lonnen, Rana Topf, Maya Saibil, Helen R Hoogenboom, Bart W |
author_sort | Leung, Carl |
collection | PubMed |
description | 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: http://dx.doi.org/10.7554/eLife.04247.001 |
format | Online Article Text |
id | pubmed-4381977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43819772015-04-03 Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin Leung, Carl Dudkina, Natalya V Lukoyanova, Natalya Hodel, Adrian W Farabella, Irene Pandurangan, Arun P Jahan, Nasrin Pires Damaso, Mafalda Osmanović, Dino Reboul, Cyril F Dunstone, Michelle A Andrew, Peter W Lonnen, Rana Topf, Maya Saibil, Helen R Hoogenboom, Bart W eLife Biophysics and Structural Biology 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: http://dx.doi.org/10.7554/eLife.04247.001 eLife Sciences Publications, Ltd 2014-12-02 /pmc/articles/PMC4381977/ /pubmed/25457051 http://dx.doi.org/10.7554/eLife.04247 Text en © 2014, Leung et al http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Biophysics and Structural Biology Leung, Carl Dudkina, Natalya V Lukoyanova, Natalya Hodel, Adrian W Farabella, Irene Pandurangan, Arun P Jahan, Nasrin Pires Damaso, Mafalda Osmanović, Dino Reboul, Cyril F Dunstone, Michelle A Andrew, Peter W Lonnen, Rana Topf, Maya Saibil, Helen R Hoogenboom, Bart W Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin |
title | Stepwise visualization of membrane pore formation by suilysin, a
bacterial cholesterol-dependent cytolysin |
title_full | Stepwise visualization of membrane pore formation by suilysin, a
bacterial cholesterol-dependent cytolysin |
title_fullStr | Stepwise visualization of membrane pore formation by suilysin, a
bacterial cholesterol-dependent cytolysin |
title_full_unstemmed | Stepwise visualization of membrane pore formation by suilysin, a
bacterial cholesterol-dependent cytolysin |
title_short | Stepwise visualization of membrane pore formation by suilysin, a
bacterial cholesterol-dependent cytolysin |
title_sort | stepwise visualization of membrane pore formation by suilysin, a
bacterial cholesterol-dependent cytolysin |
topic | Biophysics and Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381977/ https://www.ncbi.nlm.nih.gov/pubmed/25457051 http://dx.doi.org/10.7554/eLife.04247 |
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