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Immune system PDB id
2i07
Jmol
Contents
Protein chains
630 a.a. *
901 a.a. *
Ligands
NAG-NAG-MAN
NAG
* Residue conservation analysis
PDB id:
2i07
Name: Immune system
Title: Human complement component c3b
Structure: Complement c3b. Chain: a. Complement c3b. Chain: b
Source: Homo sapiens. Human. Organism_taxid: 9606. Secretion: serum. Secretion: serum
Biol. unit: Dimer (from PQS)
Resolution:
4.00Å     R-factor:   0.275     R-free:   0.323
Authors: B.J.C.Janssen,A.Christodoulidou,A.Mccarthy,J.D.Lambris,P.Gro
Key ref:
B.J.Janssen et al. (2006). Structure of C3b reveals conformational changes that underlie complement activity. Nature, 444, 213-216. PubMed id: 17051160 DOI: 10.1038/nature05172
Date:
10-Aug-06     Release date:   24-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01024  (CO3_HUMAN) -  Complement C3
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1663 a.a.
630 a.a.
Protein chain
Pfam   ArchSchema ?
P01024  (CO3_HUMAN) -  Complement C3
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1663 a.a.
901 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biochemical function     protein binding     2 terms  

 

 
DOI no: 10.1038/nature05172 Nature 444:213-216 (2006)
PubMed id: 17051160  
 
 
Structure of C3b reveals conformational changes that underlie complement activity.
B.J.Janssen, A.Christodoulidou, A.McCarthy, J.D.Lambris, P.Gros.
 
  ABSTRACT  
 
Resistance to infection and clearance of cell debris in mammals depend on the activation of the complement system, which is an important component of innate and adaptive immunity. Central to the complement system is the activated form of C3, called C3b, which attaches covalently to target surfaces to amplify complement response, label cells for phagocytosis and stimulate the adaptive immune response. C3b consists of 1,560 amino-acid residues and has 12 domains. It binds various proteins and receptors to effect its functions. However, it is not known how C3 changes its conformation into C3b and thereby exposes its many binding sites. Here we present the crystal structure at 4-A resolution of the activated complement protein C3b and describe the conformational rearrangements of the 12 domains that take place upon proteolytic activation. In the activated form the thioester is fully exposed for covalent attachment to target surfaces and is more than 85 A away from the buried site in native C3 (ref. 5). Marked domain rearrangements in the alpha-chain present an altered molecular surface, exposing hidden and cryptic sites that are consistent with known putative binding sites of factor B and several complement regulators. The structural data indicate that the large conformational changes in the proteolytic activation and regulation of C3 take place mainly in the first conversion step, from C3 to C3b. These insights are important for the development of strategies to treat immune disorders that involve complement-mediated inflammation.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Structure of C3b at 4-Å resolution.
Figure 1 : Structure of C3b at 4-|[Aring]| resolution. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com-
a, Ribbon representation in two views of C3b coloured by domain and labelled accordingly. Also indicated are the exposed thioester moiety (red spheres), anchor region (grey) and 'NT (black). For comparison, the ribbon representation of C3 and cartoons of the domain arrangements in C3b and C3 are added. b, Electron density (2mF[obs] – DF[calc], [calc]) contoured at 1 of the 'NT region with domains as indicated; density maps for each domain are given in Supplementary Fig. 1. The proteolytic steps of C3 conversion are shown schematically. 		Figure 4.
Figure 4: Proposed model for the conformational pathway of C3.
Figure 4 : Proposed model for the conformational pathway of C3. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com-
Shown schematically are the four stages: C3, C3b with C3a, iC3b with C3f and C3dg with C3c (see also Supplementary Fig. 2). These conformational changes determine the binding affinities towards soluble proteins (for example, factor B, properdin and factor H) and cell-surface receptors (for example, CR1-4, CRIg, DAF and MCP) that underlie the biological activity.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2006, 444, 213-216) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21317894 H.P.Morgan, C.Q.Schmidt, M.Guariento, B.S.Blaum, D.Gillespie, A.P.Herbert, D.Kavanagh, H.D.Mertens, D.I.Svergun, C.M.Johansson, D.Uhrín, P.N.Barlow, and J.P.Hannan (2011).
Structural basis for engagement by complement factor H of C3b on a self surface.
  Nat Struct Mol Biol, 18, 463-470.  
21527715 J.M.van den Elsen, and D.E.Isenman (2011).
A crystal structure of the complex between human complement receptor 2 and its ligand C3d.
  Science, 332, 608-611.  
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
21285368 T.Kajander, M.J.Lehtinen, S.Hyvärinen, A.Bhattacharjee, E.Leung, D.E.Isenman, S.Meri, A.Goldman, and T.S.Jokiranta (2011).
Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement.
  Proc Natl Acad Sci U S A, 108, 2897-2902.
PDB code: 2xqw
21070093 U.R.Nilsson, L.Funke, B.Nilsson, and K.N.Ekdahl (2011).
Two conformational forms of target-bound iC3b that distinctively bind complement receptors 1 and 2 and two specific monoclonal antibodies.
  Ups J Med Sci, 116, 26-33.  
20467445 D.Serruto, R.Rappuoli, M.Scarselli, P.Gros, and J.A.van Strijp (2010).
Molecular mechanisms of complement evasion: learning from staphylococci and meningococci.
  Nat Rev Microbiol, 8, 393-399.  
21205667 F.Forneris, D.Ricklin, J.Wu, A.Tzekou, R.S.Wallace, J.D.Lambris, and P.Gros (2010).
Structures of C3b in complex with factors B and D give insight into complement convertase formation.
  Science, 330, 1816-1820.  
20876141 H.Chen, D.Ricklin, M.Hammel, B.L.Garcia, W.J.McWhorter, G.Sfyroera, Y.Q.Wu, A.Tzekou, S.Li, B.V.Geisbrecht, V.L.Woods, and J.D.Lambris (2010).
Allosteric inhibition of complement function by a staphylococcal immune evasion protein.
  Proc Natl Acad Sci U S A, 107, 17621-17626.  
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.  
20133685 N.S.Laursen, N.Gordon, S.Hermans, N.Lorenz, N.Jackson, B.Wines, E.Spillner, J.B.Christensen, M.Jensen, F.Fredslund, M.Bjerre, L.Sottrup-Jensen, J.D.Fraser, and G.R.Andersen (2010).
Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus.
  Proc Natl Acad Sci U S A, 107, 3681-3686.
PDB codes: 3kls 3km9
20053731 P.K.Mallik, K.Nishikawa, A.J.Millis, and H.Shi (2010).
Commandeering a biological pathway using aptamer-derived molecular adaptors.
  Nucleic Acids Res, 38, e93.  
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
20976186 Y.Shen, N.Tolić, T.Liu, R.Zhao, B.O.Petritis, M.A.Gritsenko, D.G.Camp, R.J.Moore, S.O.Purvine, F.J.Esteva, and R.D.Smith (2010).
Blood peptidome-degradome profile of breast cancer.
  PLoS One, 5, e13133.  
  20157352 A.Goto, M.Akahori, H.Okamoto, M.Minami, N.Terauchi, Y.Haruhata, M.Obazawa, T.Noda, M.Honda, A.Mizota, M.Tanaka, T.Hayashi, M.Tanito, N.Ogata, and T.Iwata (2009).
Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population.
  J Ocul Biol Dis Infor, 2, 164-175.  
19218189 A.Yamaguchi, H.Takagawa, H.Iwakaji, S.Miyagawa, P.C.Wang, and N.Ishii (2009).
Construction of the plasmid, expression by Chinese hamster ovary cell, purification and characterization of the first three short consensus repeat modules of human complement receptor type 1.
  J Biochem, 145, 533-542.  
20033014 B.Borrell (2009).
Fraud rocks protein community.
  Nature, 462, 970.  
19574954 B.J.Janssen, L.Gomes, R.I.Koning, D.I.Svergun, A.J.Koster, D.C.Fritzinger, C.W.Vogel, and P.Gros (2009).
Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex.
  EMBO J, 28, 2469-2478.
PDB codes: 3hrz 3hs0
19833734 B.Li, H.Xi, L.Diehl, W.P.Lee, L.Sturgeon, J.Chinn, L.Deforge, R.F.Kelley, C.Wiesmann, M.van Lookeren Campagne, and S.S.Sidhu (2009).
Improving therapeutic efficacy of a complement receptor by structure-based affinity maturation.
  J Biol Chem, 284, 35605-35611.  
19168221 D.D.Despriet, C.M.van Duijn, B.A.Oostra, A.G.Uitterlinden, A.Hofman, A.F.Wright, J.B.ten Brink, A.Bakker, P.T.de Jong, J.R.Vingerling, A.A.Bergen, and C.C.Klaver (2009).
Complement component C3 and risk of age-related macular degeneration.
  Ophthalmology, 116, 474.  
19625656 D.Ricklin, A.Tzekou, B.L.Garcia, M.Hammel, W.J.McWhorter, G.Sfyroera, Y.Q.Wu, V.M.Holers, A.P.Herbert, P.N.Barlow, B.V.Geisbrecht, and J.D.Lambris (2009).
A molecular insight into complement evasion by the staphylococcal complement inhibitor protein family.
  J Immunol, 183, 2565-2574.  
19503104 J.Wu, Y.Q.Wu, D.Ricklin, B.J.Janssen, J.D.Lambris, and P.Gros (2009).
Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.
  Nat Immunol, 10, 728-733.
PDB code: 2wii
19196712 K.J.Katschke, S.Stawicki, J.Yin, M.Steffek, H.Xi, L.Sturgeon, P.E.Hass, K.M.Loyet, L.Deforge, Y.Wu, M.van Lookeren Campagne, and C.Wiesmann (2009).
Structural and Functional Analysis of a C3b-specific Antibody That Selectively Inhibits the Alternative Pathway of Complement.
  J Biol Chem, 284, 10473-10479.
PDB code: 3g6j
19402090 M.A.Cole, S.E.Tully, A.W.Dodds, J.N.Arnold, G.E.Boldt, R.B.Sim, J.Offer, and P.Wentworth (2009).
A chemical approach to immunoprotein engineering: chemoselective functionalization of thioester proteins in their native state.
  Chembiochem, 10, 1340-1343.  
19503103 S.H.Rooijakkers, J.Wu, M.Ruyken, R.van Domselaar, K.L.Planken, A.Tzekou, D.Ricklin, J.D.Lambris, B.J.Janssen, J.A.van Strijp, and P.Gros (2009).
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor.
  Nat Immunol, 10, 721-727.
PDB code: 2win
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
  19025129 D.Ricklin, and J.D.Lambris (2008).
Compstatin: a complement inhibitor on its way to clinical application.
  Adv Exp Med Biol, 632, 273-292.  
18096230 F.Bexborn, P.O.Andersson, H.Chen, B.Nilsson, and K.N.Ekdahl (2008).
The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb).
  Mol Immunol, 45, 2370-2379.  
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
18252712 H.G.Hocking, A.P.Herbert, D.Kavanagh, D.C.Soares, V.P.Ferreira, M.K.Pangburn, D.Uhrín, and P.N.Barlow (2008).
Structure of the N-terminal region of complement factor H and conformational implications of disease-linked sequence variations.
  J Biol Chem, 283, 9475-9487.
PDB codes: 2rlp 2rlq
18456336 M.C.Schuster, D.Ricklin, K.Papp, K.S.Molnar, S.J.Coales, Y.Hamuro, G.Sfyroera, H.Chen, M.S.Winters, and J.D.Lambris (2008).
Dynamic structural changes during complement C3 activation analyzed by hydrogen/deuterium exchange mass spectrometry.
  Mol Immunol, 45, 3142-3151.  
18697741 N.Doan, and P.G.Gettins (2008).
{alpha}-Macroglobulins Are Present in Some Gram-negative Bacteria: CHARACTERIZATION OF THE {alpha}2-MACROGLOBULIN FROM ESCHERICHIA COLI.
  J Biol Chem, 283, 28747-28756.  
18687868 N.Haspel, D.Ricklin, B.V.Geisbrecht, L.E.Kavraki, and J.D.Lambris (2008).
Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d.
  Protein Sci, 17, 1894-1906.
PDB codes: 3d5r 3d5s
18821684 N.K.Banda, A.K.Wood, K.Takahashi, B.Levitt, P.M.Rudd, L.Royle, J.L.Abrahams, G.L.Stahl, V.M.Holers, and W.P.Arend (2008).
Initiation of the alternative pathway of murine complement by immune complexes is dependent on N-glycans in IgG antibodies.
  Arthritis Rheum, 58, 3081-3089.  
18064050 P.Gros, F.J.Milder, and B.J.Janssen (2008).
Complement driven by conformational changes.
  Nat Rev Immunol, 8, 48-58.  
18796626 V.Frémeaux-Bacchi, E.C.Miller, M.K.Liszewski, L.Strain, J.Blouin, A.L.Brown, N.Moghal, B.S.Kaplan, R.A.Weiss, K.Lhotta, G.Kapur, T.Mattoo, H.Nivet, W.Wong, S.Gie, B.Hurault de Ligny, M.Fischbach, R.Gupta, R.Hauhart, V.Meunier, C.Loirat, M.A.Dragon-Durey, W.H.Fridman, B.J.Janssen, T.H.Goodship, and J.P.Atkinson (2008).
Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.
  Blood, 112, 4948-4952.  
17467263 A.DeWan, M.B.Bracken, and J.Hoh (2007).
Two genetic pathways for age-related macular degeneration.
  Curr Opin Genet Dev, 17, 228-233.  
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
17687277 B.J.Janssen, R.J.Read, A.T.Brünger, and P.Gros (2007).
Crystallography: crystallographic evidence for deviating C3b structure.
  Nature, 448, E1.  
  17675493 C.Q.Nguyen, H.Kim, J.G.Cornelius, and A.B.Peck (2007).
Development of Sjogren's syndrome in nonobese diabetic-derived autoimmune-prone C57BL/6.NOD-Aec1Aec2 mice is dependent on complement component-3.
  J Immunol, 179, 2318-2329.  
17989689 D.Ricklin, and J.D.Lambris (2007).
Complement-targeted therapeutics.
  Nat Biotechnol, 25, 1265-1275.  
17310251 F.J.Milder, L.Gomes, A.Schouten, B.J.Janssen, E.G.Huizinga, R.A.Romijn, W.Hemrika, A.Roos, M.R.Daha, and P.Gros (2007).
Factor B structure provides insights into activation of the central protease of the complement system.
  Nat Struct Mol Biol, 14, 224-228.
PDB code: 2ok5
17351618 M.Hammel, G.Sfyroera, D.Ricklin, P.Magotti, J.D.Lambris, and B.V.Geisbrecht (2007).
A structural basis for complement inhibition by Staphylococcus aureus.
  Nat Immunol, 8, 430-437.
PDB codes: 2gom 2gox
17699522 M.Hammel, G.Sfyroera, S.Pyrpassopoulos, D.Ricklin, K.X.Ramyar, M.Pop, Z.Jin, J.D.Lambris, and B.V.Geisbrecht (2007).
Characterization of Ehp, a secreted complement inhibitory protein from Staphylococcus aureus.
  J Biol Chem, 282, 30051-30061.
PDB code: 2noj
17590164 M.van Lookeren Campagne, C.Wiesmann, and E.J.Brown (2007).
Macrophage complement receptors and pathogen clearance.
  Cell Microbiol, 9, 2095-2102.  
17445829 P.Roversi, O.Lissina, S.Johnson, N.Ahmat, G.C.Paesen, K.Ploss, W.Boland, M.A.Nunn, and S.M.Lea (2007).
The structure of OMCI, a novel lipocalin inhibitor of the complement system.
  J Mol Biol, 369, 784-793.
PDB codes: 2cm4 2cm9
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
17989688 R.P.Rother, S.A.Rollins, C.F.Mojcik, R.A.Brodsky, and L.Bell (2007).
Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria.
  Nat Biotechnol, 25, 1256-1264.  
17051146 M.Carroll (2006).
Immunology: exposure of an executioner.
  Nature, 444, 159-160.  
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.  
17687278 , (0).
  , 0, 0.  
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.