C1q Human

C1q is a 460 kDa protein complex formed from 18 peptide chains, which are organized into three subunits of six chains each. These subunits are designated as A, B, and C chains. Each subunit consists of a Y-shaped pair of triple peptide helices joined at the stem and ending in a globular non-helical head . The A, B, and C chains are arranged in the order A-C-B on chromosome 1 .

The structure of C1q is characterized by a distinctive ‘globular domain’ of about 140 amino acids situated at the carboxyl terminus of a collagen ‘stalk’. These globular domains form a characteristic superstructure in which three protomers trimerize to form a collagen triple helix, and these trimers multimerize to form a 'bouquet’ .

C1q, along with C1r and C1s, forms the C1 complex. This complex is responsible for initiating the classical complement pathway. The classical pathway is activated when C1q binds to antibodies that are complexed with antigens. This binding causes a conformational change in the C1 complex, leading to the activation of C1r and subsequently C1s, which are serine proteases .

C1q can also bind directly to the surface of certain pathogens, triggering complement activation in the absence of antibodies. This ability to bind directly to pathogens highlights its role in the innate immune response .

C1q plays a vital role in the clearance of apoptotic cells and immune complexes. It specifically binds to apoptotic bodies of human keratinocytes, vascular endothelial cells, and lymphocytes. Complement components C1q and bound C3 mediate the clearance of these apoptotic bodies, thereby preventing the stimulation of the immune system by autoantigens .

Deficiencies in C1q are associated with various autoimmune diseases, such as systemic lupus erythematosus (SLE). Patients with SLE often have deficient expression of C1q, which impairs the clearance of apoptotic cells and immune complexes, leading to the development of autoimmunity .