EMD-0110
Consensus map of the Membrane Attack Complex
EMD-0110
Single-particle4.9 Å
Deposition: 06/07/2018Map released: 19/12/2018
Last modified: 26/12/2018
Sample Organism:
Homo sapiens
Sample: Membrane Attack Complex
Deposition Authors: Menny A, Serna M, Boyd CB, Gardener S, Joseph AP, Topf M, Bubeck D
Sample: Membrane Attack Complex
Deposition Authors: Menny A, Serna M, Boyd CB, Gardener S, Joseph AP, Topf M, Bubeck D
CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.
Menny A 
,
Serna M ,
Boyd CM,
Gardner S ,
Joseph AP,
Morgan BP ,
Topf M ,
Brooks NJ ,
Bubeck D
(2018) Nat Commun , 9 , 5316 - 5316
,
Serna M ,
Boyd CM,
Gardner S ,
Joseph AP,
Morgan BP ,
Topf M ,
Brooks NJ ,
Bubeck D
(2018) Nat Commun , 9 , 5316 - 5316
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.
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.