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TitleComplement is activated by IgG hexamers assembled at the cell surface.
Journal, issue, pagesScience, Vol. 343, Issue 6176, Page 1260-1263, Year 2014
Publish dateMar 14, 2014
AuthorsChristoph A Diebolder / Frank J Beurskens / Rob N de Jong / Roman I Koning / Kristin Strumane / Margaret A Lindorfer / Marleen Voorhorst / Deniz Ugurlar / Sara Rosati / Albert J R Heck / Jan G J van de Winkel / Ian A Wilson / Abraham J Koster / Ronald P Taylor / Erica Ollmann Saphire / Dennis R Burton / Janine Schuurman / Piet Gros / Paul W H I Parren /
PubMed AbstractComplement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies ...Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade. The interactions between neighboring Fc segments could be manipulated to block, reconstitute, and enhance complement activation and killing of target cells, using all four human IgG subclasses. We offer a general model for understanding antibody-mediated complement activation and the design of antibody therapeutics with enhanced efficacy.
External linksScience / PubMed:24626930 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution22.0 - 66.0 Å
Structure data

EMDB-2506:
Cryo-electron tomography average of an C1-IgG complex
Method: EM (subtomogram averaging) / Resolution: 66.0 Å

EMDB-2507:
Cryo-electron tomography average of an C1-IgG complex
Method: EM (subtomogram averaging) / Resolution: 66.0 Å

EMDB-2554:
electron tomography average of an IgG hexamer
Method: EM (subtomogram averaging) / Resolution: 22.0 Å

Source
  • Capra hircus (goat)
  • Homo sapiens (human)

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