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

 

 

 

 

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Contents
Protein chains
638 a.a. *
901 a.a. *
507 a.a. *
84 a.a. *
Ligands
NAG-NAG-BMA-BMA ×4
NAG-NAG-BMA-BMA-
BMA ×2
NAG-NAG-BMA-BMA-
BMA-BMA
NAG-NAG-MAN-MAN
NAG-NAG-MAN ×2
NAG-NAG
NAG-NAG-MAN-MAN-
MAN
NAG-NAG-BMA
MAN
BMA ×2
NAG
Metals
_MG ×4
Waters ×8
* Residue conservation analysis
PDB id:
2win
Name: Immune system
Title: C3 convertase (c3bbb) stabilized by scin
Structure: Complement c3 beta chain. Chain: a, c, e, g. Fragment: complement c3b beta chain, residues 23-667. Complement c3b alpha' chain. Chain: b, d, f, h. Fragment: complement c3b alpha' chain, residues 749-1663. Complement factor b. Chain: i, j, k, l. Fragment: complement factor b bb fragment, residues 260-764.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_variant: gnti-. Expression_system_cell_line: hek293es. Staphylococcus aureus. Organism_taxid: 1280.
Resolution:
3.90Å     R-factor:   0.253     R-free:   0.268
Authors: J.Wu,B.J.Janssen,P.Gros
Key ref: S.H.Rooijakkers et al. (2009). Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nat Immunol, 10, 721-727. PubMed id: 19503103
Date:
13-May-09     Release date:   09-Jun-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01024  (CO3_HUMAN) -  Complement C3 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1663 a.a.
638 a.a.
Protein chains
Pfam   ArchSchema ?
P01024  (CO3_HUMAN) -  Complement C3 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1663 a.a.
901 a.a.
Protein chains
Pfam   ArchSchema ?
P00751  (CFAB_HUMAN) -  Complement factor B from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		764 a.a.
507 a.a.
Protein chains
Q6GFB4  (SCIN_STAAR) -  Staphylococcal complement inhibitor from Staphylococcus aureus (strain MRSA252)
Seq:
Struc: 		116 a.a.
84 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains I, J, K, L: E.C.3.4.21.47  - alternative-complement-pathway C3/C5 convertase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cleaves C3 in the alpha-chain to yield C3a and C3b. Cleaves C5 in the alpha-chain to yield C5a and C5b. Both cleavages take place at the C-terminal of an arginine residue.

 

 
Nat Immunol 10:721-727 (2009)
PubMed id: 19503103  
 
 
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor.
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, P.Gros.
 
  ABSTRACT  
 
Activation of the complement system generates potent chemoattractants and leads to the opsonization of cells for immune clearance. Short-lived protease complexes cleave complement component C3 into anaphylatoxin C3a and opsonin C3b. Here we report the crystal structure of the C3 convertase formed by C3b and the protease fragment Bb, which was stabilized by the bacterial immune-evasion protein SCIN. The data suggest that the proteolytic specificity and activity depend on the formation of dimers of C3 with C3b of the convertase. SCIN blocked the formation of a productive enzyme-substrate complex. Irreversible dissociation of the complex of C3b and Bb is crucial to complement regulation and was determined by slow binding kinetics of the Mg(2+)-adhesion site in Bb. Understanding the mechanistic basis of the central complement-activation step and microbial immune evasion strategies targeting this step will aid in the development of complement therapeutics.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21055811 E.A.Clark, S.Crennell, A.Upadhyay, A.V.Zozulya, J.D.Mackay, D.I.Svergun, S.Bagby, and J.M.van den Elsen (2011).
A structural basis for Staphylococcal complement subversion: X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d.
  Mol Immunol, 48, 452-462.
PDB codes: 2wy7 2wy8
20062962 A.Laarman, F.Milder, J.van Strijp, and S.Rooijakkers (2010).
Complement inhibition by gram-positive pathogens: molecular mechanisms and therapeutic implications.
  J Mol Med, 88, 115-120.  
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.  
20150412 N.J.ten Broeke-Smits, T.E.Pronk, I.Jongerius, O.Bruning, F.R.Wittink, T.M.Breit, J.A.van Strijp, A.C.Fluit, and C.H.Boel (2010).
Operon structure of Staphylococcus aureus.
  Nucleic Acids Res, 38, 3263-3274.  
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
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.  
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.  
19800693 H.Qu, D.Ricklin, and J.D.Lambris (2009).
Recent developments in low molecular weight complement inhibitors.
  Mol Immunol, 47, 185-195.  
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.

 

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