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PDBsum entry 1q0p
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protein metals links
Hydrolase PDB id
1q0p

 

 

 

 

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Contents
Protein chain
192 a.a. *
Metals
_MN
Waters ×192
* Residue conservation analysis
PDB id:
1q0p
Name: Hydrolase
Title: A domain of factor b
Structure: Complement factor b. Chain: a. Fragment: sequence database residues 254-476. Synonym: c3/c5 convertase, properdin factor b, glycine-rich beta glycoprotein, gbg, pbf2. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: bf. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
1.80Å     R-factor:   0.210     R-free:   0.259
Authors: A.A.Bhattacharya,R.C.Liddington
Key ref:
A.A.Bhattacharya et al. (2004). Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation. Structure, 12, 371-378. PubMed id: 15016353 DOI: 10.1016/j.str.2004.02.012
Date:
17-Jul-03     Release date:   30-Mar-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00751  (CFAB_HUMAN) -  Complement factor B from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		764 a.a.
192 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: 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.

 

 
DOI no: 10.1016/j.str.2004.02.012 Structure 12:371-378 (2004)
PubMed id: 15016353  
 
 
Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation.
A.A.Bhattacharya, M.L.Lupher, D.E.Staunton, R.C.Liddington.
 
  ABSTRACT  
 
Complement factor B is a 90 kDa protein consisting of three domains: a three-module complement control protein, a von Willebrand factor A domain, and a C-terminal serine protease (SP) domain that adopts a default inactive (zymogen) conformation. The interaction between factor B and pathogen-bound C3b is mediated by its A domain, triggering a conformational change in factor B that ultimately creates the "C3 convertase" of the alternative complement pathway. We report the crystal structure of the A domain from factor B and show that it contains an integrin-like MIDAS motif that adopts the "open" conformation typical of integrin-ligand complexes, with an acidic residue (provided by a fortuitous crystal contact) completing the coordination of the metal ion. Modeling studies indicate that the factor B A domain can also adopt the closed conformation, supporting the hypothesis that an "integrin-like switch" is conserved in complement proteins and perhaps in 60 other A domains found within the human proteome.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Conformation of the MIDAS Motif and the bF-a7 Turn(A) Superposition of the MIDAS motifs of factor B and a2 integrin A domains. The structures are superposed on their central b sheets. Color-coding is as follows: factor B Ca, green; side chains, black; ligand mimetic, gold and red; a2 A domain Ca and side chains, white (semitransparent). The metal ion ("M") is in purple, with coordinating oxygens from S253, S255, T328, and two water molecules ("W") in red. The side chains of D251 and D364 form water-mediated bonds to the metal ion.(B) Overlay of the bF-a7 turns of factor B (red) with the open (translucent green) and closed (yellow) conformations of the integrin aM I domain. The Ca positions of analogous residues (M433 in factor B; F302 in aM) are indicated.
 
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 371-378) copyright 2004.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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
18936178 M.Y.Go, E.M.Chow, and J.Mogridge (2009).
The cytoplasmic domain of anthrax toxin receptor 1 affects binding of the protective antigen.
  Infect Immun, 77, 52-59.  
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
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
17921140 G.T.Le, G.Abbenante, and D.P.Fairlie (2007).
Profiling the enzymatic properties and inhibition of human complement factor B.
  J Biol Chem, 282, 34809-34816.  
17881354 M.Fresquet, T.A.Jowitt, J.Ylöstalo, P.Coffey, R.S.Meadows, L.Ala-Kokko, D.J.Thornton, and M.D.Briggs (2007).
Structural and functional characterization of recombinant matrilin-3 A-domain and implications for human genetic bone diseases.
  J Biol Chem, 282, 34634-34643.  
17234210 V.Krishnan, Y.Xu, K.Macon, J.E.Volanakis, and S.V.Narayana (2007).
The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement.
  J Mol Biol, 367, 224-233.
PDB codes: 2odp 2odq
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
16402415 J.E.Banham, C.R.Timmel, R.J.Abbott, S.M.Lea, and G.Jeschke (2006).
The characterization of weak protein-protein interactions: evidence from DEER for the trimerization of a von Willebrand Factor A domain in solution.
  Angew Chem Int Ed Engl, 45, 1058-1061.  
17098186 T.A.Springer (2006).
Complement and the multifaceted functions of VWA and integrin I domains.
  Structure, 14, 1611-1616.  
15342015 G.Hauptmann, and S.Bahram (2004).
Genetics of the central MHC.
  Curr Opin Immunol, 16, 668-672.  
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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