PDBsum entry 2b39

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Immune system PDB id
Protein chains
1610 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Structure of mammalian c3 with an intact thioester at 3a res
Structure: C3. Chain: a, b
Source: Bos taurus. Cattle. Organism_taxid: 9913
3.00Å     R-factor:   0.278     R-free:   0.286
Authors: F.Fredslund,L.Jenner,L.B.Husted,J.Nyborg,G.R.Andersen,L.Sott Jensen
Key ref:
F.Fredslund et al. (2006). The structure of bovine complement component 3 reveals the basis for thioester function. J Mol Biol, 361, 115-127. PubMed id: 16831446 DOI: 10.1016/j.jmb.2006.06.009
20-Sep-05     Release date:   13-Jun-06    
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Protein chains
Pfam   ArchSchema ?
Q2UVX4  (CO3_BOVIN) -  Complement C3
1661 a.a.
1610 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     inflammatory response   2 terms 
  Biochemical function     endopeptidase inhibitor activity     1 term  


DOI no: 10.1016/j.jmb.2006.06.009 J Mol Biol 361:115-127 (2006)
PubMed id: 16831446  
The structure of bovine complement component 3 reveals the basis for thioester function.
F.Fredslund, L.Jenner, L.B.Husted, J.Nyborg, G.R.Andersen, L.Sottrup-Jensen.
The third component of complement (C3) is a 190 kDa glycoprotein essential for eliciting the complement response. The protein consists of two polypeptide chains (alpha and beta) held together with a single disulfide bridge. The beta-chain is composed of six MG domains, one of which is shared with the alpha-chain. The disulfide bridge connecting the chains is positioned in the shared MG domain. The alpha-chain consists of the anaphylatoxin domain, three MG domains, a CUB domain, an alpha(6)/alpha(6)-barrel domain and the C-terminal C345c domain. An internal thioester in the alpha-chain of C3 (present in C4 but not in C5) is cleaved during complement activation. This mediates covalent attachment of the activated C3b to immune complexes and invading microorganisms, thereby opsonizing the target. We present the structure of bovine C3 determined at 3 Angstroms resolution. The structure shows that the ester is buried deeply between the thioester domain and the properdin binding domain, in agreement with the human structure. This domain interface is broken upon activation, allowing nucleophile access. The structure of bovine C3 clearly demonstrates that the main chain around the thioester undergoes a helical transition upon activation. This rearrangement is proposed to be the basis for the high level of reactivity of the thioester group. A strictly conserved glutamate residue is suggested to function catalytically in thioester proteins. Structure-based design of inhibitors of C3 activation may target a conserved pocket between the alpha-chain and the beta-chain of C3, which appears essential for conformational changes in C3.
  Selected figure(s)  
Figure 1.
Figure 1. Overall structure of native C3. (a) Ribbon representation of the molecule with the domains coloured individually and labelled. The Asn938 glycan, the linker region, and the thioester are labelled G, L and T, respectively. The thioester domain is labelled TED. (b) View towards the concave surface of C3 (c) Close-up on the “valley” formed by the MG1–MG6 domains and the linker region at the concave face. The domains are coloured in the same manner in the following Figures.
Figure 5.
Figure 5. Hydrogen bonding and thioester integrity. (a) The main chain hydrogen bond pattern around the thioester in bovine C3. Except for the thioester, only main chain atoms are shown. Hydrogen bonds from the carbonyl group of Met1014 to the amide groups of either Met1017 or Thr1018 appear to be almost equally favorable. (b) The same area in C3d. In this structure (RCSB entry 1C3D), a Cys1010Ala mutant was used. (c) The hydrogen bond patterns in native human C3 (RCSB entry 2A73) around the thioester in the same orientation as in (a). (d) The hydrogen bond pattern of human C4Adg (RCSB entry 1HZF) in the same area.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 361, 115-127) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21217642 N.S.Laursen, K.R.Andersen, I.Braren, E.Spillner, L.Sottrup-Jensen, and G.R.Andersen (2011).
Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex.
  EMBO J, 30, 606-616.
PDB codes: 3prx 3pvm
20418421 D.J.Sukovich, J.L.Seffernick, J.E.Richman, J.A.Gralnick, and L.P.Wackett (2010).
Widespread head-to-head hydrocarbon biosynthesis in bacteria and role of OleA.
  Appl Environ Microbiol, 76, 3850-3862.  
20418444 D.J.Sukovich, J.L.Seffernick, J.E.Richman, K.A.Hunt, J.A.Gralnick, and L.P.Wackett (2010).
Structure, function, and insights into the biosynthesis of a head-to-head hydrocarbon in Shewanella oneidensis strain MR-1.
  Appl Environ Microbiol, 76, 3842-3849.  
20666732 K.Li, J.Gor, and S.J.Perkins (2010).
Self-association and domain rearrangements between complement C3 and C3u provide insight into the activation mechanism of C3.
  Biochem J, 431, 63-72.  
20826443 R.H.Baxter, S.Steinert, Y.Chelliah, G.Volohonsky, E.A.Levashina, and J.Deisenhofer (2010).
A heterodimeric complex of the LRR proteins LRIM1 and APL1C regulates complement-like immunity in Anopheles gambiae.
  Proc Natl Acad Sci U S A, 107, 16817-16822.
PDB codes: 3o53 3o6n 3oja
20124699 W.J.Cook, N.Galakatos, W.C.Boyar, R.L.Walter, and S.E.Ealick (2010).
Structure of human desArg-C5a.
  Acta Crystallogr D Biol Crystallogr, 66, 190-197.
PDB codes: 3hqa 3hqb
19368894 V.Krishnan, K.Ponnuraj, Y.Xu, K.Macon, J.E.Volanakis, and S.V.Narayana (2009).
The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb.
  Structure, 17, 611-619.
PDB code: 3frp
18536718 F.Fredslund, N.S.Laursen, P.Roversi, L.Jenner, C.L.Oliveira, J.S.Pedersen, M.A.Nunn, S.M.Lea, R.Discipio, L.Sottrup-Jensen, and G.R.Andersen (2008).
Structure of and influence of a tick complement inhibitor on human complement component 5.
  Nat Immunol, 9, 753-760.
PDB code: 3cu7
18064050 P.Gros, F.J.Milder, and B.J.Janssen (2008).
Complement driven by conformational changes.
  Nat Rev Immunol, 8, 48-58.  
17684013 B.J.Janssen, E.F.Halff, J.D.Lambris, and P.Gros (2007).
Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition.
  J Biol Chem, 282, 29241-29247.
PDB code: 2qki
17606907 R.H.Baxter, C.I.Chang, Y.Chelliah, S.Blandin, E.A.Levashina, and J.Deisenhofer (2007).
Structural basis for conserved complement factor-like function in the antimalarial protein TEP1.
  Proc Natl Acad Sci U S A, 104, 11615-11620.
PDB code: 2pn5
17051150 C.Wiesmann, K.J.Katschke, J.Yin, K.Y.Helmy, M.Steffek, W.J.Fairbrother, S.A.McCallum, L.Embuscado, L.DeForge, P.E.Hass, and M.van Lookeren Campagne (2006).
Structure of C3b in complex with CRIg gives insights into regulation of complement activation.
  Nature, 444, 217-220.
PDB codes: 2icc 2ice 2icf
17027507 F.J.Milder, H.C.Raaijmakers, M.D.Vandeputte, A.Schouten, E.G.Huizinga, R.A.Romijn, W.Hemrika, A.Roos, M.R.Daha, and P.Gros (2006).
Structure of complement component C2A: implications for convertase formation and substrate binding.
  Structure, 14, 1587-1597.
PDB codes: 2i6q 2i6s
17172439 N.Nishida, T.Walz, and T.A.Springer (2006).
Structural transitions of complement component C3 and its activation products.
  Proc Natl Acad Sci U S A, 103, 19737-19742.  
17098186 T.A.Springer (2006).
Complement and the multifaceted functions of VWA and integrin I domains.
  Structure, 14, 1611-1616.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.