Complement component 1q

complement component 1, q subcomponent, A chain
Identifiers
Symbol	C1QA
Entrez	712
HUGO	1241
OMIM	120550
RefSeq	NM_015991
UniProt	P02745
Other data
Locus	Chr. 1 p36.3-34.1

complement component 1, q subcomponent, B chain
Identifiers
Symbol	C1QB
Entrez	713
HUGO	1242
OMIM	120570
RefSeq	NM_000491
UniProt	P02746
Other data
Locus	Chr. 1 p36.3-34.1

complement component 1, q subcomponent, C chain
Identifiers
Symbol	C1QC
Alt. symbols	C1QG
Entrez	714
HUGO	1245
OMIM	120575
RefSeq	NM_172369
UniProt	P02747
Other data
Locus	Chr. 1 p36.11

The complement component 1q (C1q) is a protein complex involved in the complement system, which is part of the innate immune system. C1q is part of the C1-complex.

Antibodies of the adaptive immune system can bind antigen, forming an antigen-antibody complex. When C1q binds antibody-antigen complexes, the C1-complex is activated. Activation of the C1-complex intitiates the classical complement pathway of the complement system. Only 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, isoleucine, or hydroxylysine; they, therefore, strongly resemble collagen fibrils.

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.

Function

File:Complement pathway.svg

The classical and alternative complement pathways. C1q is the orange part of the C1-complex at the top of the image.

It is assumed that the globular ends are the sites for multivalent attachment to the complement fixing sites in immune complexed immunoglobulin. Patients suffering from 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 suffer from SLE. C1q may also play a central role in the aging of cells.

C1q associates with C1r and C1s in order to yield the C1-complex (C1qr²s²), the first component of the serum complement system. Deficiency of C1q has been associated with lupus erythematosus and glomerulonephritis.

It is potentially multivalent for attachment to the complement fixation sites of immunoglobulin. 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.

Further reading

• C1q: structure, function, and receptors. Kishore U1, Reid KB. Immunopharmacology. 2000 Aug;49(1-2):159-70.
• Functional Complement C1q Abnormality Leads to Impaired Immune Complexes and Apoptotic Cell Clearance.
• Deciphering the fine details of C1 assembly and activation mechanisms: “mission impossible”? - detailed diagrams

External links

• Complement+C1q at the US National Library of Medicine Medical Subject Headings (MeSH)