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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2017
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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’. |
format | Online Article Text |
id | pubmed-5483522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
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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