CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers

• DOI: 10.1038/s41467-018-07653-5
• Publication Date: 2018-12-10T12:48:05Z
• Authors: Anaïs Menny; Marina Serna; Courtney M. Boyd; Scott Gardner; Agnel Praveen Joseph; B. Paul Morgan; Maya Topf; Nicholas J. Brooks; Doryen Bubeck
• Keywords: STRUCTURAL BASIS; MECHANISM; Models, Molecular; 0301 basic medicine; 570; Protein Conformation; Image Processing; EM STRUCTURE; Science; Lipid Bilayers; INSERTION; 610; Complement Membrane Attack Complex; bcs; Article; 03 medical and health sciences; Computer-Assisted; Models; Polysaccharides; Image Processing, Computer-Assisted; Humans; Protein Interaction Domains and Motifs; C9; CELL; 0303 health sciences; Science & Technology; REFINEMENT; Spectrum Analysis; Q; Cryoelectron Microscopy; Molecular; Complement C9; Complement C8; COMPONENT; Complement C7; Complement C6; Multidisciplinary Sciences; CHOLESTEROL-DEPENDENT CYTOLYSIN; Liposomes; Science & Technology - Other Topics; CD59

Abstract The membrane attack complex (MAC) is one of the immune system’s first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis self-cells. How MAC disrupts barrier remains unclear. Here we use electron cryo-microscopy flicker spectroscopy show interacts with lipid bilayers in two distinct ways. Whereas C6 C7 associate outer leaflet reduce energy for bending, C8 C9 traverse bilayer increasing rigidity. CryoEM reconstructions reveal plasticity pore demonstrate how C5b6 acts as a platform, directing assembly giant β-barrel whose structure supported by glycan scaffold. Our work provides structural basis understanding β-pore forming breach reveals mechanism kills regulates cell functions.