The complement component 1q (or simply C1q) is a

protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein ...

involved in the complement system, which is part of the innate immune system. C1q together with C1r and C1s form the

C1 complex The C1 complex (''complement component 1'', ''C1'') is a protein complex involved in the complement system. It is the first component of the classical complement pathway and is composed of the subcomponents C1q, C1r and C1s. Structure The C ...

. Antibodies of the

adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

can bind

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

, forming an

antigen-antibody complex An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen o ...

. When C1q binds antigen-antibody complexes, the

becomes activated. Activation of the C1 complex initiates the

classical complement pathway The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and ...

of the complement system. The antibodies

IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...

and all

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

subclasses except

IgG4 Immunoglobulin G (Ig G) is a Antibody#Classes, type of antibody. Representing approximately 75% of blood plasma, serum immunoglobulins, antibodies in humans, IgG is the most common type of antibody found in Circulatory system, blood circulation. I ...

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 Hydroxylysine (Hyl) is an amino acid with the molecular formula C6H14N2O3. It was first discovered in 1921 by Donald Van Slyke Donald Dexter Van Slyke (March 29, 1883 – May 4, 1971) was a Dutch American biochemist. His achievements include ...

; 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.

Domain

The C1q domain is a conserved

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of ...

C1q The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate immune system. C1q together with C1r and C1s form the C1 complex. Antibodies of the adaptive immune system can bi ...

is a subunit of the C1

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

that activates the serum complement system. C1q comprises 6 A, 6 B and 6 C chains. These share the same topology, each possessing a small, globular N-terminal 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

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s and shows

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...

and structural similarity to collagens 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. C1q associates with C1r and C1s in order to yield the

(''C1qr²s²''), the first component of the serum complement system. Deficiency of C1q has been associated with

lupus erythematosus Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...

and

glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...

. It is potentially

multivalent In chemistry, polyvalency (or polyvalence, multivalency) is the property of chemical species (generally atoms or molecules) that exhibit more than one valence by forming multiple chemical bonds (Fig. 1). A bivalent species can form two bonds; ...

for attachment to the complement fixation sites of immunoglobulin. The sites are on the CH2 domain of

and, it is thought, on the CH4 domain of

. IgG4 cannot bind C1q, but the other three IgG types can. The appropriate

peptide sequence Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

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 In biochemistry, avidity refers to the accumulated strength of ''multiple'' affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. Avidity di ...

References

External links