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PDBsum entry 2wii
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protein ligands metals Protein-protein interface(s) links
Immune system PDB id
2wii

 

 

 

 

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Contents
Protein chains
640 a.a. *
896 a.a. *
245 a.a. *
Ligands
NAG-NAG-BMA-BMA-
BMA-BMA
GOL ×17
NAG
Metals
_CA
Waters ×172
* Residue conservation analysis
PDB id:
2wii
Name: Immune system
Title: Complement c3b in complex with factor h domains 1-4
Structure: Complement c3 beta chain. Chain: a. Fragment: residues 23-667. Synonym: complement c3, c3 and pzp-like alpha-2-macroglobulin domain- containing protein 1. Complement c3b alpha' chain. Chain: b. Fragment: residues 749-1663. Synonym: complement c3, c3 and pzp-like alpha-2-macroglobulin domain-
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293e.
Resolution:
2.70Å     R-factor:   0.218     R-free:   0.252
Authors: J.Wu,B.J.C.Janssen,P.Gros
Key ref: J.Wu et al. (2009). Structure of complement fragment C3b-factor H and implications for host protection by complement regulators. Nat Immunol, 10, 728-733. PubMed id: 19503104
Date:
12-May-09     Release date:   09-Jun-09    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01024  (CO3_HUMAN) -  Complement C3 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1663 a.a.
640 a.a.
Protein chain
Pfam   ArchSchema ?
P01024  (CO3_HUMAN) -  Complement C3 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1663 a.a.
896 a.a.
Protein chain
Pfam   ArchSchema ?
P08603  (CFAH_HUMAN) -  Complement factor H from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1231 a.a.
245 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
Nat Immunol 10:728-733 (2009)
PubMed id: 19503104  
 
 
Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.
J.Wu, Y.Q.Wu, D.Ricklin, B.J.Janssen, J.D.Lambris, P.Gros.
 
  ABSTRACT  
 
Factor H (FH) is an abundant regulator of complement activation and protects host cells from self-attack by complement. Here we provide insight into the regulatory activity of FH by solving the crystal structure of the first four domains of FH in complex with its target, complement fragment C3b. FH interacted with multiple domains of C3b, covering a large, extended surface area. The structure indicated that FH destabilizes the C3 convertase by competition and electrostatic repulsion and that FH enables proteolytic degradation of C3b by providing a binding platform for protease factor I while stabilizing the overall domain arrangement of C3b. Our results offer general models for complement regulation and provide structural explanations for disease-related mutations in the genes encoding both FH and C3b.
 

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.
PDB code: 3oxu
21270465 I.C.Pechtl, D.Kavanagh, N.McIntosh, C.L.Harris, and P.N.Barlow (2011).
Disease-associated N-terminal complement factor H mutations perturb cofactor and decay-accelerating activities.
  J Biol Chem, 286, 11082-11090.  
21270828 L.Schejbel, I.M.Schmidt, M.Kirchhoff, C.B.Andersen, H.V.Marquart, P.Zipfel, and P.Garred (2011).
Complement factor H deficiency and endocapillary glomerulonephritis due to paternal isodisomy and a novel factor H mutation.
  Genes Immun, 12, 90-99.  
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
21336275 P.Gros (2011).
In self-defense.
  Nat Struct Mol Biol, 18, 401-402.  
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
20941397 B.D.Persson, N.B.Schmitz, C.Santiago, G.Zocher, M.Larvie, U.Scheu, J.M.Casasnovas, and T.Stehle (2010).
Structure of the extracellular portion of CD46 provides insights into its interactions with complement proteins and pathogens.
  PLoS Pathog, 6, 0.
PDB code: 3o8e
19835885 C.Q.Schmidt, A.P.Herbert, H.D.Mertens, M.Guariento, D.C.Soares, D.Uhrin, A.J.Rowe, D.I.Svergun, and P.N.Barlow (2010).
The central portion of factor H (modules 10-15) is compact and contains a structurally deviant CCP module.
  J Mol Biol, 395, 105-122.
PDB code: 2kms
20720586 D.Ricklin, G.Hajishengallis, K.Yang, and J.D.Lambris (2010).
Complement: a key system for immune surveillance and homeostasis.
  Nat Immunol, 11, 785-797.  
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.
PDB codes: 2xw9 2xwa 2xwb 2xwj
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.  
20010915 J.R.Dunkelberger, and W.C.Song (2010).
Complement and its role in innate and adaptive immune responses.
  Cell Res, 20, 34-50.  
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.  
20843825 L.G.Fritsche, N.Lauer, A.Hartmann, S.Stippa, C.N.Keilhauer, M.Oppermann, M.K.Pandey, J.Köhl, P.F.Zipfel, B.H.Weber, and C.Skerka (2010).
An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD).
  Hum Mol Genet, 19, 4694-4704.  
20973636 M.H.Van Regenmortel (2010).
First Aegean International Conference on Molecular Recognition.
  Expert Rev Proteomics, 7, 639-642.  
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
20852386 R.Martínez-Barricarte, M.Heurich, F.Valdes-Cañedo, E.Vazquez-Martul, E.Torreira, T.Montes, A.Tortajada, S.Pinto, M.Lopez-Trascasa, B.P.Morgan, O.Llorca, C.L.Harris, and S.Rodríguez de Córdoba (2010).
Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation.
  J Clin Invest, 120, 3702-3712.  
20044478 S.C.Nilsson, I.Nita, L.Månsson, T.W.Groeneveld, L.A.Trouw, B.O.Villoutreix, and A.M.Blom (2010).
Analysis of binding sites on complement factor I that are required for its activity.
  J Biol Chem, 285, 6235-6245.  
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.  
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 code is shown on the right.

 

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