6FCZ

Model of gC1q-Fc complex based on 7A EM map

Summary for 6FCZ

• Entry DOI: 10.2210/pdb6fcz/pdb
• EMDB information: 4231 4232
• Descriptor: Complement C1q subcomponent subunit A, Complement C1q subcomponent subunit B, Complement C1q subcomponent subunit C, ... (5 entities in total)
• Functional Keywords: complement, antibody, complex, c1, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 93068.24

Authors

Ugurlar, D.,Howes, S.C.,de Kreuk, B.J.K.,de Jong, R.N.,Beurskens, F.J.,Koster, A.J.,Parren, P.W.H.I.,Sharp, T.H.,Gros, P.,Koning, R.I. (deposition date: 2017-12-21, release date: 2018-02-28, Last modification date: 2024-11-13)

Primary citation

Ugurlar, D.,Howes, S.C.,de Kreuk, B.J.,Koning, R.I.,de Jong, R.N.,Beurskens, F.J.,Schuurman, J.,Koster, A.J.,Sharp, T.H.,Parren, P.W.H.I.,Gros, P.
Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement.
Science, 359:794-797, 2018

PubMed Abstract: Danger patterns on microbes or damaged host cells bind and activate C1, inducing innate immune responses and clearance through the complement cascade. How these patterns trigger complement initiation remains elusive. Here, we present cryo-electron microscopy analyses of C1 bound to monoclonal antibodies in which we observed heterogeneous structures of single and clustered C1-immunoglobulin G1 (IgG1) hexamer complexes. Distinct C1q binding sites are observed on the two Fc-CH2 domains of each IgG molecule. These are consistent with known interactions and also reveal additional interactions, which are supported by functional IgG1-mutant analysis. Upon antibody binding, the C1q arms condense, inducing rearrangements of the C1rs proteases and tilting C1q's cone-shaped stalk. The data suggest that C1r may activate C1s within single, strained C1 complexes or between neighboring C1 complexes on surfaces.

PubMed: 29449492
DOI: 10.1126/science.aao4988

Experimental method

ELECTRON MICROSCOPY (10 Å)