title: Trimeric reassembly of the globular domain of human C1q.
abstract: C1q is a versatile recognition protein which binds to a variety of targets and consequently triggers the classical pathway of complement. C1q is a hetero-trimer composed of three chains (A, B and C) arranged in three domains, a short N-terminal region, followed by a collagenous repeat domain that gives rise to the formation of (ABC) triple helices, each ending in a C-terminal hetero-trimeric globular domain, called gC1q, which is responsible for the recognition properties of C1q. The mechanism of the trimeric assembly of C1q and in particular the role of each domain in the process is unknown. Here, we have investigated if the gC1q domain was able to assemble into functional trimers, in vitro, in the absence of the collagenous domain, a motif known to promote obligatory trimers in other proteins. Acid-mediated gC1q protomers reassembled into functional trimers, once neutralized, indicating that it is the gC1q domain which possesses the information for trimerization. However, reassembly occurred after neutralization, only if the gC1q protomers had preserved a residual tertiary structure at the end of the acidic treatment. Thus, the collagenous domain of C1q might initialize the folding of the gC1q domain so that subsequent assembly of the entire molecule can occur.
authors.affiliation: Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale, CEA-CNRS-Université Joseph Fourier, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Tacnet
authors.forename: Eric Chung Chee
authors.initials: EC
authors.lastname: Cheong
authors.forename: Pierrette
authors.initials: P
authors.lastname: Goeltz
authors.forename: Berhane
authors.initials: B
authors.lastname: Ghebrehiwet
authors.forename: Gérard J
authors.initials: GJ
authors.lastname: Arlaud
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Liu
authors.forename: Claire
authors.initials: C
authors.lastname: Lesieur
mesh_terms: D003094:Collagen / Q000737:chemistry; D015922:Complement C1q / Q000737:chemistry*; D006801:Humans; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D015922:Complement C1q; D003094:Collagen