Complement component C1q (460 kDa) associates with the proenzymes C1r and C1s (found as a Ca2+-dependent 360 kDa C1r2C1S2 complex) to yield complement C1, the first component of the serum complement system. Electron-microscopy studies have shown C1q to be composed of six globular heads linked via six collagen-like stalks to a fibril-like central region.
The complement component C1q is composed of three chains: the C1qA, C1qB and C1qC chains encoded by the C1qA (MIM*120550), C1qB (MIM*120570) and C1qC (MIM*120575) genes, respectively, which are located in the directions A, C and B on chromosome 1p36.2-p34.1. Each chain is encoded by two exons and has a collagen-like region and a globular domain. The macromolecular structure of C1q is a tulip-like structure generated by assembly of six A, six B and six C chains, with a collagen-like region as part of the stalk, and the C1q globular region as part of the 'tulip heads'. Every tulip head consists of the globular domains from one A, one B and one C chain, each with different ligand-binding specificities. The collagen-like regions of complement component C1q interact with the Ca2+-dependent C1r2C1s2 proenzyme complex, and efficient activation of complement component C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Complement component C1q synthesis has been reported in several different cells, including hepatocytes, Kupffer cells, macrophages, dendritic cells, microglial cells, fibroblasts, epithelial cells of the small intestine and newborn foreskin epidermal keratinocytes, but recent studies suggest that bone marrow-derived mononuclear cells may be the major source of complement component C1q in plasma.
Besides its role as an initiator of the classical complement activation pathway, complement C1q has several other possible functions, as recently reviewed by Nayak et al. It can bind to early apoptotic cells and facilitate phagocytosis, and may also participate in clearance of late-apoptotic cells via IgM/C1q-mediated classical pathway activation. It can induce dendritic cell maturation via C1q receptors on the immature dendritic cells, it may modulate T lymphocytes, which have been shown to express C1q receptors, and C1q is suspected to participate in the negative selection of autoreactive B cells. In addition, C1q has been suggested to be implicated in neuronal synapse modification and to have a part in the early stages of pregnancy.
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