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The mystery behind membrane insertion: a review of the complement membrane attack complex

The membrane attack complex (MAC) is an important innate immune effector of the complement terminal pathway that forms cytotoxic pores on the surface of microbes. Despite many years of research, MAC structure and mechanism of action have remained elusive, relying heavily on modelling and inference f...

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Detalles Bibliográficos
Autores principales: Bayly-Jones, Charles, Bubeck, Doryen, Dunstone, Michelle A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483522/
https://www.ncbi.nlm.nih.gov/pubmed/28630159
http://dx.doi.org/10.1098/rstb.2016.0221
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author Bayly-Jones, Charles
Bubeck, Doryen
Dunstone, Michelle A.
author_facet Bayly-Jones, Charles
Bubeck, Doryen
Dunstone, Michelle A.
author_sort Bayly-Jones, Charles
collection PubMed
description The membrane attack complex (MAC) is an important innate immune effector of the complement terminal pathway that forms cytotoxic pores on the surface of microbes. Despite many years of research, MAC structure and mechanism of action have remained elusive, relying heavily on modelling and inference from biochemical experiments. Recent advances in structural biology, specifically cryo-electron microscopy, have provided new insights into the molecular mechanism of MAC assembly. Its unique ‘split-washer’ shape, coupled with an irregular giant β-barrel architecture, enable an atypical mechanism of hole punching and represent a novel system for which to study pore formation. This review will introduce the complement terminal pathway that leads to formation of the MAC. Moreover, it will discuss how structures of the pore and component proteins underpin a mechanism for MAC function, modulation and inhibition. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.
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spelling pubmed-54835222017-06-26 The mystery behind membrane insertion: a review of the complement membrane attack complex Bayly-Jones, Charles Bubeck, Doryen Dunstone, Michelle A. Philos Trans R Soc Lond B Biol Sci Articles The membrane attack complex (MAC) is an important innate immune effector of the complement terminal pathway that forms cytotoxic pores on the surface of microbes. Despite many years of research, MAC structure and mechanism of action have remained elusive, relying heavily on modelling and inference from biochemical experiments. Recent advances in structural biology, specifically cryo-electron microscopy, have provided new insights into the molecular mechanism of MAC assembly. Its unique ‘split-washer’ shape, coupled with an irregular giant β-barrel architecture, enable an atypical mechanism of hole punching and represent a novel system for which to study pore formation. This review will introduce the complement terminal pathway that leads to formation of the MAC. Moreover, it will discuss how structures of the pore and component proteins underpin a mechanism for MAC function, modulation and inhibition. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’. The Royal Society 2017-08-05 2017-06-19 /pmc/articles/PMC5483522/ /pubmed/28630159 http://dx.doi.org/10.1098/rstb.2016.0221 Text en © 2017 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Articles
Bayly-Jones, Charles
Bubeck, Doryen
Dunstone, Michelle A.
The mystery behind membrane insertion: a review of the complement membrane attack complex
title The mystery behind membrane insertion: a review of the complement membrane attack complex
title_full The mystery behind membrane insertion: a review of the complement membrane attack complex
title_fullStr The mystery behind membrane insertion: a review of the complement membrane attack complex
title_full_unstemmed The mystery behind membrane insertion: a review of the complement membrane attack complex
title_short The mystery behind membrane insertion: a review of the complement membrane attack complex
title_sort mystery behind membrane insertion: a review of the complement membrane attack complex
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483522/
https://www.ncbi.nlm.nih.gov/pubmed/28630159
http://dx.doi.org/10.1098/rstb.2016.0221
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