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Complement component 3

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Title: Complement component 3  
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Complement component 3

Complement component 3
PDB rendering based on 1c3d.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; AHUS5; ARMD9; ASP; C3a; C3b; CPAMD1; HEL-S-62p
External IDs ChEMBL: GeneCards:
EC number
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3.[1][2]

Contents

  • Function 1
  • Structure 2
  • Clinical use 3
  • Interactions 4
  • References 5
  • Further reading 6
  • External links 7

Function

C3 plays a central role in the activation of complement system.[3] Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are susceptible to bacterial infection.[4][5]

One form of C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the proteolytic cleavage of C3 into C3a and C3b, generated during activation through the classical pathway as well as the lectin pathway. C3a is an anaphylotoxin and the precursor of some cytokines such as ASP, and C3b serves as an opsonizing agent. Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing B cell responses. In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and factor B (Bb). Once C3 is activated to C3b, it exposes a reactive thioester that allows the peptide to covalently attach to any surface that can provide a nucleophile such as a primary amine or a hydroxyl group. Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase.

C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay-accelerating factor (DAF) activity. Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease that performs these cuts but it requires the help of another protein (Factor H, CR1, MCP or C4BP) to supply cofactor activity.

Structure

Several crystallographic structures of C3 have been determined[6] and reveal that this protein contains 13 domains.[7][8][9][10]

Clinical use

Complement tests
C4 (C) FB (A) C3 CH50 Conditions
 · PSG, C3 NeF AA
 ·  · HA, C4D
 ·  ·  · TCPD
 · /↓ SLE
inflammation

Levels of C3 in the blood may be measured to support or refute a particular medical diagnosis. For example, low C3 levels are associated with some types of kidney disease such as post-infectious glomerulonephritis, membranoproliferative glomerulonephritis, and shunt nephritis.

Interactions

Complement component 3 has been shown to interact with Factor H.[11][12]

References

  1. ^ de Bruijn MH, Fey GH (February 1985). "Human complement component C3: cDNA coding sequence and derived primary structure". Proc. Natl. Acad. Sci. U.S.A. 82 (3): 708–12.  
  2. ^ "Entrez Gene: C3 complement component 3". 
  3. ^ Sahu A, Lambris JD (April 2001). "Structure and biology of complement protein C3, a connecting link between innate and acquired immunity". Immunol. Rev. 180: 35–48.  
  4. ^ Lachmann P (December 1975). "Genetics of the complement system". J. Med. Genet. 12 (4): 372–7.  
  5. ^ Matsuyama W, Nakagawa M, Takashima H, Muranaga F, Sano Y, Osame M (December 2001). "Molecular analysis of hereditary deficiency of the third component of complement (C3) in two sisters". Intern. Med. 40 (12): 1254–8.  
  6. ^ "Advanced search results for UniProt accession P01024". Protein Data Bank in Europe (PDBe). European Bioinformatics Institute. Retrieved 2010-12-27. 
  7. ^ Janssen BJ, Huizinga EG, Raaijmakers HC, Roos A, Daha MR, Nilsson-Ekdahl K, Nilsson B, Gros P (September 2005). "Structures of complement component C3 provide insights into the function and evolution of immunity". Nature 437 (7058): 505–11.  
  8. ^ Janssen BJ, Christodoulidou A, McCarthy A, Lambris JD, Gros P (November 2006). "Structure of C3b reveals conformational changes that underlie complement activity". Nature 444 (7116): 213–6.  
  9. ^ Wiesmann C, Katschke KJ, Yin J, Helmy KY, Steffek M, Fairbrother WJ, McCallum SA, Embuscado L, DeForge L, Hass PE, van Lookeren Campagne M (November 2006). "Structure of C3b in complex with CRIg gives insights into regulation of complement activation". Nature 444 (7116): 217–20.  
  10. ^ Fredslund F, Jenner L, Husted LB, Nyborg J, Andersen GR, Sottrup-Jensen L (August 2006). "The structure of bovine complement component 3 reveals the basis for thioester function". J. Mol. Biol. 361 (1): 115–27.  
  11. ^ Soames CJ, Sim RB (September 1997). "Interactions between human complement components factor H, factor I and C3b". Biochem. J. 326 ( Pt 2): 553–61.  
  12. ^ Jokiranta TS, Westin J, Nilsson UR, Nilsson B, Hellwage J, Löfås S, Gordon DL, Ekdahl KN, Meri S (March 2001). "Complement C3b interactions studied with surface plasmon resonance technique". Int. Immunopharmacol. 1 (3): 495–506.  

Further reading

  • Bradley DT, Zipfel PF, Hughes AE (June 2011). "Complement in age-related macular degeneration: a focus on function". Eye (Lond) 25 (6): 683–93.  

External links

  • GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome
  • OMIM entries on Atypical Hemolytic-Uremic Syndrome
  • GeneReviews/NCBI/NIH/UW entry on Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II
  • Complement C3 at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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