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TitleCryoEM reveals how the complement membrane attack complex ruptures lipid bilayers.
Journal, issue, pagesNat Commun, Vol. 9, Issue 1, Page 5316, Year 2018
Publish dateDec 14, 2018
AuthorsAnaïs Menny / Marina Serna / Courtney M Boyd / Scott Gardner / Agnel Praveen Joseph / B Paul Morgan / Maya Topf / Nicholas J Brooks / Doryen Bubeck /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:30552328 / PubMed Central
MethodsEM (single particle)
Resolution4.4 - 5.9 Å
Structure data

EMDB-0106, PDB-6h03:
OPEN CONFORMATION OF THE MEMBRANE ATTACK COMPLEX
Method: EM (single particle) / Resolution: 5.6 Å

EMDB-0107, PDB-6h04:
Closed conformation of the Membrane Attack Complex
Method: EM (single particle) / Resolution: 5.6 Å

EMDB-0109:
Asymmetric region of the Membrane Attack Complex in the closed conformation
Method: EM (single particle) / Resolution: 5.9 Å

EMDB-0110:
Consensus map of the Membrane Attack Complex
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-0111:
Asymmetric region of the Membrane Attack Complex in the open conformation
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-0112:
Hinge region of the Membrane Attack Complex in the open conformation
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-0113:
C9 oligomer region of the Membrane Attack Complex in the open conformation
Method: EM (single particle) / Resolution: 4.4 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • Human (human)
KeywordsIMMUNE SYSTEM / C5B9

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