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

机译:膜插入背后的奥秘:补体膜攻击复合体的综述

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摘要

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’.
机译:膜攻击复合物(MAC)是补体末端途径的重要先天免疫效应物,可在微生物表面形成细胞毒性孔。尽管进行了多年的研究,但MAC的结构和作用机理仍然难以捉摸,严重依赖于生化实验的建模和推论。结构生物学的最新进展,特别是冷冻电子显微镜,为MAC组装的分子机理提供了新见解。其独特的“分离垫圈”形状,加上不规则的巨型β桶式结构,可实现非常规的打孔机制,并代表了一种研究孔形成的新颖系统。本文将介绍导致MAC形成的补体末端途径。此外,还将讨论孔和成分蛋白的结构如何支撑MAC功能,调节和抑制的机制。本文是“膜孔:从结构和组装到医学和技术”主题的一部分。

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