CryoEM Reveals How the Complement Membrane Attack Complex Ruptures Lipid Bilayers

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Dec 16

PMID 30552328

Citations 55

Authors

Anais Menny

Marina Serna

Courtney M Boyd

Scott Gardner

Agnel Praveen Joseph

B Paul Morgan

Maya Topf

Nicholas J Brooks

Doryen Bubeck

Affiliations

Soon will be listed here.

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 of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant β-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how β-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions.

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