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

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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’.

Original languageEnglish
Article number20160221
Number of pages9
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Issue number1726
Publication statusPublished - 5 Aug 2017


  • Cholesterol-dependent cytolysin
  • Complement pathway
  • Membrane attack complex
  • Pore-forming toxins
  • Poreforming protein

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