The complement component 1q (or simply C1q) is a protein complex involved in the

complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...

, which is part of the

innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

. C1q together with

C1r Complement C1r subcomponent (, ''activated complement C1r'', ''C overbar 1r esterase'', ''C1r'') is a protein involved in the complement system of the innate immune system. In humans, C1r is encoded by the ''C1R'' gene. C1r along with C1q and C1 ...

and

C1s Complement component 1s (, '' C1 esterase'', ''activated complement C1s'', ''complement C overbar 1r'', ''C1s'') is a protein involved in the complement system. C1s is part of the C1 complex. In humans, it is encoded by the ''C1S'' gene. C1s cle ...

form the C1 complex.

Antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

of the adaptive immune system can bind antigen, forming an antigen-antibody complex. When C1q binds antigen-antibody complexes, the C1 complex becomes activated. Activation of the C1 complex initiates the classical complement pathway of the complement system. The antibodies IgM and all IgG subclasses except IgG4 are able to initiate the complement system.

Structure

C1q is a 400 kDa protein formed from 18 peptide chains in 3 subunits of 6. Each 6 peptide subunit consists of a Y-shaped pair of triple peptide helices joined at the stem and ending in a globular non-helical head. The 80-amino acid helical component of each triple peptide contain many Gly-X-Y sequences, where X and Y are

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprot ...

, or hydroxylysine; they, therefore, strongly resemble

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

fibrils Fibrils (from the Latin ''fibra'') are structural biological materials found in nearly all living organisms. Not to be confused with fibers or filaments, fibrils tend to have diameters ranging from 10-100 nanometers (whereas fibers are micro ...

C1q chains A, B and C

C1q is composed of 18 polypeptide chains: six A-chains, six B-chains, and six C-chains. Each chain contains a collagen-like region located near the N terminus and a C-terminal globular region. The A-, B-, and C-chains are arranged in the order A-C-B on chromosome 1.

Domain

The C1q domain is a conserved protein domain. C1q is a subunit of the C1 enzyme complex that activates the

serum Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...

. C1q comprises 6 A, 6 B and 6 C

chain A chain is a serial assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a rope in that it is flexible and curved in compression but linear, rigid, and load-bearing in tension. A c ...

s. These share the same topology, each possessing a small, globular

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

domain, a collagen-like Gly/Pro-rich central region, and a conserved C-terminal region, the C1q domain. The C1q protein is produced in collagen-producing cells and shows sequence and structural similarity to

s VIII and X.

Function

It is assumed that the globular ends are the sites for multivalent attachment to the complement fixing sites in immune complexed immunoglobulin. Patients with Lupus erythematosus often have deficient expression of C1q. Genetic deficiency of C1q is extremely rare (approximately 75 known cases) although the majority (>90%) of those have

SLE Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...

. C1q associates with C1r and C1s in order to yield the C1 complex (''C1qr²s²''), the first component of the serum

. Deficiency of C1q has been associated with lupus erythematosus and glomerulonephritis. It is potentially multivalent for attachment to the complement fixation sites of

immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

. The sites are on the CH2 domain of IgG and, it is thought, on the CH4 domain of IgM. IgG4 cannot bind C1q, but the other three IgG types can. The appropriate peptide sequence of the complement fixing site might become exposed following complexing of the immunoglobulin, or the sites might always be available, but might require multiple attachment by C1q with critical geometry in order to achieve the necessary avidity.

References

External links