title: Structural and functional anatomy of the globular domain of complement protein C1q.
abstract: C1q is the first subcomponent of the classical pathway of the complement system and a major connecting link between innate and acquired immunity. As a versatile charge pattern recognition molecule, C1q is capable of engaging a broad range of ligands via its heterotrimeric globular domain (gC1q) which is composed of the C-terminal regions of its A (ghA), B (ghB) and C (ghC) chains. Recent studies using recombinant forms of ghA, ghB and ghC have suggested that the gC1q domain has a modular organization and each chain can have differential ligand specificity. The crystal structure of the gC1q, molecular modeling and protein engineering studies have combined to illustrate how modular organization, charge distribution and the spatial orientation of the heterotrimeric assembly offer versatility of ligand recognition to C1q. Although the biochemical and structural studies have provided novel insights into the structure-function relationships within the gC1q domain, they have also raised many unexpected issues for debate.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK. ukishore@hotmail.com
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
authors.forename: Rohit
authors.initials: R
authors.lastname: Ghai
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Greenhough
authors.forename: Annette K
authors.initials: AK
authors.lastname: Shrive
authors.forename: Domenico M
authors.initials: DM
authors.lastname: Bonifati
authors.forename: Mihaela G
authors.initials: MG
authors.lastname: Gadjeva
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.forename: Mihaela S
authors.initials: MS
authors.lastname: Kojouharova
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Alok
authors.initials: A
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D015922:Complement C1q / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D007074:Immunoglobulin G; D015922:Complement C1q; D002097:C-Reactive Protein