title: Recent progress in the understanding of the structure-function relationships of the globular head regions of C1q.
abstract: The first step in the activation of the classical pathway of complement cascade by immune complexes involves the binding of the C-terminal globular head regions of C1q to the Fc regions of IgG or IgM, each globular head being composed of the C-terminal halves of one A-, one B- and one C-chain. Recent studies using recombinant forms of globular region appear to suggest that each globular head of C1q may be composed of three, structurally and functionally, independent domains/modules. The heterotrimeric organisation thus could offer functional flexibility and versatility to the whole C1q molecule. The crystal structure of an adipocyte-specific serum protein, Acrp-30, has revealed the existence of a structural fold shared by members of a new C1q/tumor necrosis factor (TNF) superfamily, characterized by a distinctive globular domain. The protein members seem to be active as self-assembling noncovalent trimers, whose individual chains fold as compact 'jellyroll' beta sandwiches. The recognition of a C1q/TNF superfamily, which has wide-ranging functions, highlights the possibility that the globular regions of C1q may fulfill more binding functions than previously envisaged.
authors.affiliation: Department of Biochemistry, and Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, United Kingdom. ukishore@hammer.imm.ox.ac.uk
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
authors.forename: Mihaela S
authors.initials: MS
authors.lastname: Kojouharova
authors.forename: Kenneth B M
authors.initials: KB
authors.lastname: Reid
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015922:Complement C1q / Q000737:chemistry* / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
chemical_list: D007136:Immunoglobulins; D011994:Recombinant Proteins; D015922:Complement C1q