C1 complex

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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. [1] [2] [3]

Contents

Structure

The C1 complex is ~790 kDa and is composed of 1 molecule of C1q, 2 molecules of C1r and 2 molecules of C1s, or C1qr2s2. [2] [3] [4]

Function

The classical and alternative complement pathways. Complement pathway.svg
The classical and alternative complement pathways.

Activation of the C1 complex initiates the classical complement pathway. This occurs when C1q binds to antigen-antibody complexes. The antibodies IgM or certain subclasses of IgG complexed with antigens are able to initiate the complement system: a single pentameric IgM can initiate the pathway, while several monomeric IgG molecules are needed. [3] C1q can also be activated in other ways, for example by binding to pentraxins such as C-reactive protein [2] or directly to the surface of pathogens. [1]

Such binding of C1q leads to conformational changes in the C1q molecule, which activates the associated C1r molecules. Active C1r cleaves the C1s molecules, activating them. Active C1s splits C4 and then C2, producing C4a, C4b, C2a and C2b. The classical pathway C3-convertase (C4bC2b complex) is created, which promotes cleavage of C3. [1]

Related Research Articles

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

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 pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellular bacteria, protozoa, helminths, and fungi which could cause serious problems to the health of the host organism if not cleared from the body.

Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Complement system</span> Part of the immune system that enhances the ability of antibodies and phagocytic cells

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 attack the pathogen's cell membrane. It is part of the innate immune system, which is not adaptable and does not change during an individual's lifetime. The complement system can, however, be recruited and brought into action by antibodies generated by the adaptive immune system.

<span class="mw-page-title-main">Classical complement pathway</span> Aspect of the immune system

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 IgM.

<span class="mw-page-title-main">C3-convertase</span>

C3 convertase belongs to family of serine proteases and is necessary in innate immunity as a part of the complement system which eventuate in opsonisation of particles, release of inflammatory peptides, C5 convertase formation and cell lysis.

Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed by phagocytes. Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens, cancer cells, aged cells, dead or dying cells, excess synapses, or protein aggregates. Opsonins help clear pathogens, as well as dead, dying and diseased cells.

<span class="mw-page-title-main">C5-convertase</span> Serine protease that plays key role in innate immunity.

C5 convertase is an enzyme belonging to a family of serine proteases that play key role in the innate immunity. It participates in the complement system ending with cell death.

<span class="mw-page-title-main">Lectin pathway</span>

The lectin pathway or MBL pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade. In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The lectin pathway starts with mannose-binding lectin (MBL) or ficolin binding to certain sugars.

<span class="mw-page-title-main">B-cell receptor</span> Transmembrane protein on the surface of a B cell

The B-cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B-cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, and is typically located on the outer surface of these lymphocyte cells. Through biochemical signaling and by physically acquiring antigens from the immune synapses, the BCR controls the activation of the B cell. B cells are able to gather and grab antigens by engaging biochemical modules for receptor clustering, cell spreading, generation of pulling forces, and receptor transport, which eventually culminates in endocytosis and antigen presentation. B cells' mechanical activity adheres to a pattern of negative and positive feedbacks that regulate the quantity of removed antigen by manipulating the dynamic of BCR–antigen bonds directly. Particularly, grouping and spreading increase the relation of antigen with BCR, thereby proving sensitivity and amplification. On the other hand, pulling forces delinks the antigen from the BCR, thus testing the quality of antigen binding.

<span class="mw-page-title-main">Complement component 2</span> Protein-coding gene in the species Homo sapiens

Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine protease. Deficiency of C2 has been associated with certain autoimmune diseases.

<span class="mw-page-title-main">Complement component 1r</span> Protein-coding gene in the species Homo sapiens

Complement C1r subcomponent is a protein involved in the complement system of the innate immune system. In humans, C1r is encoded by the C1R gene.

<span class="mw-page-title-main">Complement component 1s</span> Protein-coding gene in the species Homo sapiens

Complement component 1s is a protein involved in the complement system. C1s is part of the C1 complex. In humans, it is encoded by the C1S gene.

<span class="mw-page-title-main">Complement component 1q</span> Protein complex

The complement component 1q 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.

Complement component 4 (C4), in humans, is a protein involved in the intricate complement system, originating from the human leukocyte antigen (HLA) system. It serves a number of critical functions in immunity, tolerance, and autoimmunity with the other numerous components. Furthermore, it is a crucial factor in connecting the recognition pathways of the overall system instigated by antibody-antigen (Ab-Ag) complexes to the other effector proteins of the innate immune response. For example, the severity of a dysfunctional complement system can lead to fatal diseases and infections. Complex variations of it can also lead to schizophrenia. The C4 protein was thought to derive from a simple two-locus allelic model, which however has been replaced by a much more sophisticated multimodular RCCX gene complex model which contain long and short forms of the C4A or C4B genes usually in tandem RCCX cassettes with copy number variation, that somewhat parallels variation in the levels of their respective proteins within a population along with CYP21 in some cases depending on the number of cassettes and whether it contains the functional gene instead of pseudogenes or fragments. Originally defined in the context of the Chido/Rodgers blood group system, the C4A-C4B genetic model is under investigation for its possible role in schizophrenia risk and development.

<span class="mw-page-title-main">C3b</span>

C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B, or a C5 convertase when bound to C4b and C2b or when an additional C3b molecule binds to the C3bBb complex.

<span class="mw-page-title-main">C1QA</span> Protein-coding gene in the species Homo sapiens

Complement C1q subcomponent subunit A is a protein that in humans is encoded by the C1QA gene.

The following outline is provided as an overview of and topical guide to immunology:

<span class="mw-page-title-main">C3a (complement)</span>

C3a is one of the proteins formed by the cleavage of complement component 3; the other is C3b. C3a is a 77 residue anaphylatoxin that binds to the C3a receptor (C3aR), a class A G protein-coupled receptor. It plays a large role in the immune response.

CUB domain is an evolutionarily conserved protein domain. The CUB domain is a structural motif of approximately 110 residues found almost exclusively in extracellular and plasma membrane-associated proteins, many of which are developmentally regulated. These proteins are involved in a diverse range of functions, including complement activation, developmental patterning, tissue repair, axon guidance and angiogenesis, cell signalling, fertilisation, haemostasis, inflammation, neurotransmission, receptor-mediated endocytosis, and tumour suppression. Many CUB-containing proteins are peptidases belonging to MEROPS peptidase families M12A (astacin) and S1A (chymotrypsin).

References

  1. 1 2 3 Janeway, CA Jr; Travers P; Walport M; et al. (2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland Science. Retrieved 29 December 2017.
  2. 1 2 3 Abbas, Abul (2015). Cellular and molecular immunology. Philadelphia, PA: Elsevier Saunders. pp. 70–71. ISBN   978-0-323-28645-9.
  3. 1 2 3 A., Owen, Judith (2013). Kuby immunology. Punt, Jenni., Stranford, Sharon A., Jones, Patricia P., Kuby, Janis. (7th ed.). New York: W.H. Freeman. pp. 190–194. ISBN   9781429219198. OCLC   820117219.{{cite book}}: CS1 maint: multiple names: authors list (link)
  4. Venkatraman Girija, Umakhanth; Gingras, Alexandre R.; Marshall, Jamie E.; Panchal, Roshni; Sheikh, Md. Arif; Harper, James A. J.; Gál, Péter; Schwaeble, Wilhelm J.; Mitchell, Daniel A.; Moody, Peter C. E.; Wallis, Russell (20 August 2013). "Structural basis of the C1q/C1s interaction and its central role in assembly of the C1 complex of complement activation". Proceedings of the National Academy of Sciences. 110 (34): 13916–13920. doi:10.1073/pnas.1311113110. ISSN   0027-8424 . Retrieved 24 October 2023.

Further reading