Bayly-Jones Charles, Bubeck Doryen, Dunstone Michelle A
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton Campus, Melbourne, Victoria 3800, Australia.
ARC Centre of Excellence in Advanced Molecular Imaging, Biomedicine Discovery Institute, Monash University, Clayton Campus, Melbourne, Victoria 3800, Australia.
Philos Trans R Soc Lond B Biol Sci. 2017 Aug 5;372(1726). doi: 10.1098/rstb.2016.0221.
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'.
膜攻击复合物（MAC）是补体终末途径的一种重要先天性免疫效应物，可在微生物表面形成细胞毒性孔道。尽管经过多年研究，MAC的结构和作用机制仍不明确，很大程度上依赖于生化实验的建模和推断。结构生物学的最新进展，特别是冷冻电子显微镜技术，为MAC组装的分子机制提供了新的见解。其独特的“开口垫圈”形状，加上不规则的巨大β桶结构，促成了一种非典型的打孔机制，代表了一个研究孔形成的新系统。本综述将介绍导致MAC形成的补体终末途径。此外，还将讨论孔和组成蛋白的结构如何支撑MAC功能、调节和抑制的机制。本文是主题为“膜孔：从结构与组装到医学与技术”特刊的一部分。
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