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Anaphylotoxin-like domain |
Structure of porcine C5adesArg.[1]
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Identifiers |
Symbol |
ANATO |
Pfam |
PF01821 |
InterPro |
IPR000020 |
SMART |
ANATO |
PROSITE |
PDOC00906 |
SCOP |
1c5a |
SUPERFAMILY |
1c5a |
Available protein structures: |
Pfam |
structures |
PDB |
RCSB PDB; PDBe; PDBj |
PDBsum |
structure summary |
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Anaphylatoxins, or complement peptides, are fragments (C3a, C4a and C5a) that are produced as part of the activation of the complement system.[2] Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense.[3] They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments.[4] A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins:[4][5] they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability.[5] They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals.[5] The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulfide bridges.[5]
Contents
- 1 Function
- 2 Examples
- 3 Terminology
- 4 Human proteins containing this domain
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Function
Anaphylatoxins are able to trigger degranulation (release of substances) of endothelial cells, mast cells or phagocytes, which produce a local inflammatory response. If the degranulation is widespread, it can cause a shock-like syndrome similar to that of an allergic reaction.
Anaphylatoxins indirectly mediate:
- smooth muscle cells contraction, for example bronchospasms
- increase in the permeability of blood capillaries
- chemotaxis — receptor-mediated movement of leukocytes in the direction of the increasing concentration of anaphylatoxins
Examples
Important anaphylatoxins:
- C5a has the highest specific biological activity and is able to act directly on neutrophils and monocytes to speed up the phagocytosis of pathogens.
- C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, all of which contribute to the initiation of the adaptive immune response.
- C4a is the least active anaphylatoxin.
Terminology
Although some drugs (morphine, codeine, synthetic ACTH) and some neurotransmitters (norepinephrine, substance P) are important mediators of degranulation of mast cells or basophils, they are generally not called anaphylatoxins. This term is reserved only for fragments of the complement system.
Human proteins containing this domain
C3, C4A, C4B, C4B-1, C5, FBLN1, FBLN2
See also
- Allergy
- Anaphylatoxin receptors
- Anaphylaxis
- Complement system
- Inflammation
- Immune system
- Nervous system
References
- ^ Williamson, Michael P.; Madison, Vincent S. (1990). "Three-dimensional structure of porcine C5ades Arg from proton nuclear magnetic resonance data". Biochemistry 29 (12): 2895–905. doi:10.1021/bi00464a002. PMID 2337573.
- ^ Hugli, T. E. (1986). "Biochemistry and biology of anaphylatoxins". Complement 3 (3): 111–27. PMID 3542363.
- ^ Fritzinger, D. C.; Petrella, E. C.; Connelly, M. B.; Bredehorst, R; Vogel, C. W. (1992). "Primary structure of cobra complement component C3". Journal of immunology 149 (11): 3554–62. PMID 1431125.
- ^ a b Ogata, R. T.; Rosa, P. A.; Zepf, N. E. (1989). "Sequence of the gene for murine complement component C4". The Journal of biological chemistry 264 (28): 16565–72. PMID 2777798.
- ^ a b c d Gennaro, Renato; Simonic, Tatjana; Negri, Armando; Mottola, Cristina; Secchi, Camillo; Ronchi, Severino; Romeo, Domenico (1986). "C5a fragment of bovine complement. Purification, bioassays, amino-acid sequence and other structural studies". European Journal of Biochemistry 155 (1): 77–86. doi:10.1111/j.1432-1033.1986.tb09460.x. PMID 3081348.
Further reading
- Gerard, C; Gerard, N P (1994). "C5A Anaphylatoxin and Its Seven Transmembrane-Segment Receptor". Annual Review of Immunology 12: 775–808. doi:10.1146/annurev.iy.12.040194.004015. PMID 8011297.
- Pan, Zhixing K. (1998). "Anaphylatoxins C5a and C3a induce nuclear factor κB activation in human peripheral blood monocytes". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1443 (1–2): 90–8. doi:10.1016/S0167-4781(98)00198-5. PMID 9838061.
External links
- Anaphylatoxin at the US National Library of Medicine Medical Subject Headings (MeSH)
Immunology: lymphocytic adaptive immune system and complement
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Lymphoid |
Antigens |
- Antigen presentation/Professional APCs: Dendritic cell
- Macrophage
- B cell
- Immunogen
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Antibodies |
- Antibody
- Monoclonal antibodies
- Polyclonal antibodies
- Autoantibody
- Microantibody
- Polyclonal B cell response
- Allotype
- Isotype
- Idiotype
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Immunity vs.
tolerance |
- action: Immunity
- Autoimmunity
- Alloimmunity
- Allergy
- Hypersensitivity
- Inflammation
- Cross-reactivity
- inaction: Tolerance
- Central
- Peripheral
- Clonal anergy
- Clonal deletion
- Tolerance in pregnancy
- Immunodeficiency
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Immunogenetics |
- Affinity maturation (Somatic hypermutation
- Clonal selection)
- V(D)J recombination
- Junctional diversity
- Immunoglobulin class switching
- MHC/HLA
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Lymphocytes |
- Cellular (T cell)
- Humoral (B cell)
- NK cell
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Substances |
- Cytokines
- Opsonin
- Cytolysin
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Index of the immune system
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Description |
- Physiology
- cells
- autoantigens
- autoantibodies
- complement
- surface antigens
- IG receptors
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Disease |
- Allergies
- Immunodeficiency
- Immunoproliferative immunoglobulin disorders
- Hypersensitivity and autoimmune disorders
- Neoplasms and cancer
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Treatment |
- Procedures
- Drugs
- antihistamines
- immunostimulants
- immunosuppressants
- monoclonal antibodies
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Index of the lymphatic system
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Description |
- Anatomy
- Physiology
- Development
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Disease |
- Vessels
- Organs
- congenital
- neoplasms and cancer
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Treatment |
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This article incorporates text from the public domain Pfam and InterPro IPR000020
UpToDate Contents
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- 1. 補体系の制御因子および受容体 regulators and receptors of the complement system
- 2. 糸球体の免疫障害の機序 mechanisms of immune injury of the glomerulus
- 3. 関節リウマチの病因 pathogenesis of rheumatoid arthritis
- 4. 補体経路 complement pathways
- 5. 好中球運動の決定要因 determinants of neutrophil movement
English Journal
- Complement Is a Central Mediator of Radiotherapy-Induced Tumor-Specific Immunity and Clinical Response.
- Surace L1, Lysenko V1, Fontana AO2, Cecconi V1, Janssen H3, Bicvic A1, Okoniewski M4, Pruschy M2, Dummer R5, Neefjes J3, Knuth A6, Gupta A1, van den Broek M7.
- Immunity.Immunity.2015 Apr 13. pii: S1074-7613(15)00123-5. doi: 10.1016/j.immuni.2015.03.009. [Epub ahead of print]
- Radiotherapy induces DNA damage and cell death, but recent data suggest that concomitant immune stimulation is an integral part of the therapeutic action of ionizing radiation. It is poorly understood how radiotherapy supports tumor-specific immunity. Here we report that radiotherapy induced tumor c
- PMID 25888260
- The role of complement factor C3 in lipid metabolism.
- Barbu A1, Hamad OA2, Lind L3, Ekdahl KN2, Nilsson B2.
- Molecular immunology.Mol Immunol.2015 Mar 5. pii: S0161-5890(15)00076-0. doi: 10.1016/j.molimm.2015.02.027. [Epub ahead of print]
- Abundant reports have shown that there is a strong relationship between C3 and C3a-desArg levels, adipose tissue, and risk factors for cardiovascular disease, metabolic syndrome and diabetes. The data indicate that complement components, particularly C3, are involved in lipid metabolism. The C3 frag
- PMID 25746915
Japanese Journal
- Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza
- Ohta Rieko,Torii Yuka,Imai Masaki [他],KIMURA Hiroshi,OKADA Noriko,ITO Yoshinori
- Microbiology and immunology 55(3), 191-198, 2011-03-20
- NAID 10031121459
- アナフィラトキシン C3a,C4a,C5a (広範囲 血液・尿化学検査 免疫学的検査(第7版・3)その数値をどう読むか) -- (免疫学的検査 補体および関連物質)
Related Links
- Anaphylatoxins, or complement peptides, are fragments (C3a, C4a and C5a) that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are large glycoproteins that have important functions ...
- anaphylatoxin /ana·phyl·a·tox·in/ (-fil´ah-tok″sin) a substance produced in blood serum during complement fixation which serves as a mediator of inflammation by inducing mast cell degranulation and histamine release; on injection into ...
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