Classical antibody-mediated complement activation

Stable Identifier
R-HSA-173623
Type
Pathway
Species
Homo sapiens
Compartment
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Summation

C1, the first component of complement is a complex containing three protein species, C1q, C1r, and C1s. C1q is assembled from six identical subunits each of which consists of three homologous chains (A, B, and C). These chains form a globular domain at the C-terminus, followed by the "neck" and a coil in the "stalk." The six subunits are held together by the collagenous stalk parts (giving rise to the comparison of C1q with a "bunch of six tulips"). The stalks also interact with the [C1s:C1r:C1r:C1s] tetramer assembled in a linear chain. Binding of an antigen to an antibody of the IgM or IgG class induces a conformational change in the Fc domain of the antibody that allows it to bind to the C1q component of C1. C1 activation requires interaction with two separate Fc domains, so pentavalent IgM antibody is far more efficient at complement activation than IgG antibody. Antibody binding results in a conformational change in the C1r component of the C1 complex and a proteolytic cleavage of C1r, activating it. Active C1r then cleaves and activates the C1s component of the C1 complex (Muller-Eberhard 1988).

Literature References
PubMed ID Title Journal Year
9777414 Structural and functional studies on C1r and C1s: new insights into the mechanisms involved in C1 activity and assembly

Arlaud, GJ, Rossi, V, Thielens, NM, Gaboriaud, C, Bersch, B, Hernandez, JF

Immunobiology 1998
12788922 X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement.

Gregory, LA, Thielens, NM, Arlaud, GJ, Fontecilla-Camps, JC, Gaboriaud, C

J Biol Chem 2003
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Orthologous Events
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