
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’.
Life Sciences & Biomedicine - Other Topics, PORE-FORMING TOXIN, STRUCTURAL BASIS, CONFORMATIONAL-CHANGES, Models, Molecular, 570, pore-forming toxins, SOMATIC MUTATION, membrane attack complex, Complement Membrane Attack Complex, cholesterol-dependent cytolysin, PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA, REGULATORY PROTEIN CD59, CRYSTAL-STRUCTURE, Biology, 9TH COMPONENT, Evolutionary Biology, Science & Technology, Cell Membrane, Cryoelectron Microscopy, complement pathway, 11 Medical And Health Sciences, Articles, 06 Biological Sciences, 620, pore-forming protein, ESCHERICHIA-COLI, MACPF, Life Sciences & Biomedicine
Life Sciences & Biomedicine - Other Topics, PORE-FORMING TOXIN, STRUCTURAL BASIS, CONFORMATIONAL-CHANGES, Models, Molecular, 570, pore-forming toxins, SOMATIC MUTATION, membrane attack complex, Complement Membrane Attack Complex, cholesterol-dependent cytolysin, PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA, REGULATORY PROTEIN CD59, CRYSTAL-STRUCTURE, Biology, 9TH COMPONENT, Evolutionary Biology, Science & Technology, Cell Membrane, Cryoelectron Microscopy, complement pathway, 11 Medical And Health Sciences, Articles, 06 Biological Sciences, 620, pore-forming protein, ESCHERICHIA-COLI, MACPF, Life Sciences & Biomedicine
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