The classical complement pathway is a major element of innate immunity against infection, and is also involved in immune tolerance, graft rejection and various pathologies. This pathway is triggered by C1, a multimolecular protease formed from the association of a recognition protein, C1q, and a catalytic subunit, the calcium-dependent tetramer C1s-C1r-C1r-C1s, which comprises two copies of each of the modular proteases C1r and C1s. All activators of the pathway are recognized by the C1q moiety of C1, a process that generates a conformational signal that triggers self-activation of C1r, which in turn activates C1s, the enzyme that mediates specific cleavage of C4 and C2, the C1 substrates. Early work based on biochemical and electron microscopy studies has allowed characterization of the domain structure of the C1 subcomponents and led to a low-resolution model of the complex in which the elongated C1s-C1r-C1r-C1s tetramer folds into a compact, figure-of-8-shaped conformation upon interaction with C1q. The strategy used over the past decade was based on a dissection of the C1 proteins into modular segments to characterize their function and solve their three-dimensional structure by X-ray crystallography or NMR spectroscopy. This approach allows deep insights into the structure-function relationships of C1, particularly with respect to the assembly of the C1 complex and the mechanisms underlying its activation and proteolytic activity.
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November 2002
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Conference Article|
November 01 2002
Structural biology of Cl
G. J. Arlaud;
G. J. Arlaud
1
*Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex I, France
1To whom correspondence should be addressed (e-mail ariaud@ibs.fr)
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C. Gaboriaud;
C. Gaboriaud
†Laboratoire de Cristallographie et Cristallogénèse des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex I, France
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N. M. Thielens;
N. M. Thielens
*Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex I, France
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V. Rossi
V. Rossi
*Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex I, France
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Publisher: Portland Press Ltd
Received:
June 06 2002
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (6): 1001–1006.
Article history
Received:
June 06 2002
Citation
G. J. Arlaud, C. Gaboriaud, N. M. Thielens, V. Rossi; Structural biology of Cl. Biochem Soc Trans 1 November 2002; 30 (6): 1001–1006. doi: https://doi.org/10.1042/bst0301001
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