Complement component C5

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Complement component C5
Complement component C5
Belt model according to PDB  3CU7

Existing structure data : 3CU7

Properties of human protein
Mass / length primary structure 74/999/655 amino acids (C5a / C5bα / C5bβ)
Precursor (1676 aa)
Identifier
Gene name C5
External IDs
Occurrence
Parent taxon Chordates
Orthologue
human House mouse
Entrez 727 15139
Ensemble ENSG00000106804 ENSMUSG00000026874
UniProt P01031 P06684
Refseq (mRNA) NM_001735 NM_010406
Refseq (protein) NP_001726 NP_034536
Gene locus Chr 9: 120.95 - 121.05 Mb Chr 2: 34.98 - 35.06 Mb
PubMed search 727 15139

The complement component C5 is a protein of the complement system and, as part of the membrane attack complex, has an important function for the immune system of humans and animals. Mutations in the C5 - gene responsible for a rare hereditary immune deficiency.

The protein is structurally related to alpha-2-macroglobulin .

Genetics and Construction

The C5 for encoding C5 - gene is located in humans on chromosome 9 locus q34.1. It consists of 41 exons and occupies a total of 79,000 base pairs .

In humans, the gene product consists of 1676 amino acids . The enzyme C5 convertase splits C5 into the two components C5a (74 amino acids) and the significantly larger C5b .

C5a
Schematic representation of C5a

In humans, C5a consists of 74 amino acids and has a molar mass of 11  kDa . The polypeptide belongs to the group of anaphylatoxins and plays an important role in chemotaxis . In the blood serum , the enzyme carboxypeptidase B cleaves off the terminal amino acid arginine from C5a , creating "C5a des Arg". The activity is only slightly reduced. C5a has a number of local and systemic effects. For example, it contracts the smooth muscles , which can lead to bronchial spasms. It also increases the permeability of the blood capillaries . It releases histamine in the mast cells . C5a activates neutrophils and macrophages .

C5a can bind to two different receptors , called C5aR and C5L2, which are located on the surface of phagocytes. C5aR activates the G-protein-mediated signaling pathways via the mitogen-activated protein kinase pathway. The inhibition of C5aR has potent anti-inflammatory effects. There is currently no consensus on the function of C5L2. The results of various working groups are very contradictory.

Since tumor growth is positively influenced by C5a in the mouse animal model , the inhibition of C5a is a potential target in cancer immunotherapy .

C5b
→ see main article membrane attack complex

C5b has a molar mass of 190 kDa. It attaches itself to the cell membrane of the target cell and forms the first component of the membrane attack complex . Together with the components C6, C7, C8 and C9 that adhere to it, a pore about 10 nm in diameter is formed in the cell membrane, which leads to cytolysis of the cell.

literature

  • HD Manthey et al: Complement component 5a (C5a). In: Int J Biochem Cell Biol 41, 2009, pp. 2114-2117. PMID 19464229 (Review)
  • H. Rus et al .: C5b-9 complement complex in autoimmune demyelination: dual role in neuroinflammation and neuroprotection. In: Adv Exp Med Biol 586, 2006, pp. 139-151. PMID 16893070 (Review)
  • A. López-Lera et al .: Molecular characterization of three new mutations causing C5 deficiency in two non-related families. In: Mol Immunol 46, 2009, pp. 2340-2347. PMID 19414197

Individual evidence

  1. ↑ Homologues at inParanoid
  2. ↑ UniProt P01031
  3. ↑ SJ Jeremiah et al .: The assignment of the human gene coding for complement C5 to chromosome 9q22-9q33. In: Ann Hum Genet 52, 1988, pp. 111-116. PMID 3248005
  4. ↑ DF Carney et al .: Structural aspects of the human C5 gene: intron / exon organization, 5-prime-flanking region features, and characterization of two truncated cDNA clones. In: J Biol Chem 266, 1991, pp. 18786-18791. PMID 1917999
  5. ↑ Eentrez Protein: Complement component 5 [Homo sapiens]. Accessed December 27, 2009
  6. ↑ L. Cui, DF Carney, TE Hugli: Primary structure and functional characterization of rat C5a: an anaphylatoxin with unusually high potency. In: Protein science: a publication of the Protein Society. Volume 3, Number 8, August 1994, pp. 1169-1177, doi : 10.1002 / pro.5560030803 , PMID 7987212 , PMC 2142913 (free full text).
  7. ↑ HN Eisen: General Immunology. JB Lippincott Company, 2nd Edition, 1990, ISBN 0-397-50833-6
  8. ↑ M. Koleva: De novo induction of anaphylatoxin C5a receptors in rat hepatocytes by the inflammation trigger lipopolysaccharide in vivo mediation by the inflammation mediators Interleukin-6 and -1β Dissertation, University of Göttingen, 2001
  9. ^ PA Ward: Functions of C5a receptors. In: J Mol Med 87, 2009, pp. 375-378. PMID 19189071 (Review)
  10. ↑ MM Markiewski and JD paneling: complement Unwelcome. In: Cancer Res 69, 2009, pp. 6367-6370. PMID 19654288 (Review)

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