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J. Biol. Chem., Vol. 278, Issue 47, 46974-46982, November 21, 2003

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The Crystal Structure of the Globular Head of Complement Protein C1q Provides a Basis for Its Versatile Recognition Properties^*

Christine Gaboriaud, Jordi Juanhuix, Arnaud Gruez, Monique Lacroix¶, Claudine Darnault, David Pignol||, Denis Verger, Juan C. Fontecilla-Camps, and Gérard J. Arlaud¶**

From the Laboratoire de Cristallographie et Cristallogénse des Protéines and the ^¶Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique (CEA)-CNRSUniversité Joseph Fourier, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France,Laboratori de Llum Sincrotro, Ed. Cn, Campus UAB 08193 Bellaterra, Barcelona, Spain, and ^||Laboratoire de Bioénergétique Cellulaire, Département d'Ecophysiologie Végétale et de Microbiologie, CEA-Cadarache, 13108 Saint Paul lez Durance, France

C1q is a versatile recognition protein that binds to an amazing variety of immune and non-immune ligands and triggers activation of the classical pathway of complement. The crystal structure of the C1q globular domain responsible for its recognition properties has now been solved and refined to 1.9 Å of resolution. The structure reveals a compact, almost spherical heterotrimeric assembly held together mainly by non-polar interactions, with a Ca²⁺ ion bound at the top. The heterotrimeric assembly of the C1q globular domain appears to be a key factor of the versatile recognition properties of this protein. Plausible three-dimensional models of the C1q globular domain in complex with two of its physiological ligands, C-reactive protein and IgG, are proposed, highlighting two of the possible recognition modes of C1q. The C1q/human IgG1 model suggests a critical role for the hinge region of IgG and for the relative orientation of its Fab domain in C1q binding.

Received for publication, July 18, 2003 , and in revised form, August 29, 2003.

The atomic coordinates and structure factors (code 1PK6) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by the Commissariat à l'Energie Atomique, the CNRS, and the Université Joseph Fourier, Grenoble. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed. Tel.: 33-4-38-78-49-81; Fax: 33-4-38-78-51-22; E-mail: arlaud{at}ibs.fr.

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