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PDBsum entry 1gkg
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Complement PDB id
1gkg

 

 

 

 

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Contents
Protein chain
136 a.a. *
* Residue conservation analysis
PDB id:
1gkg
Name: Complement
Title: Structure determination and rational mutagenesis reveal binding surface of immune adherence receptor, cr1 (cd35)
Structure: Complement receptor type 1. Chain: a. Fragment: modules 16 and 17, of site 2, residue 1002-1133. Synonym: cr1, c3b/c4b receptor, cd35, antigen. Engineered: yes. Mutation: yes. Other_details: second two modules of site 2 in cr1, a c3b/c4b binding site
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Other_details: recombinant technology using human gene (not synthetic)
NMR struc: 24 models
Authors: B.O.Smith,R.L.Mallin,M.Krych-Goldberg,X.Wang,R.E.Hauhart,K.Bromek, D.Uhrin,J.P.Atkinson,P.N.Barlow
Key ref:
B.O.Smith et al. (2002). Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor. Cell, 108, 769-780. PubMed id: 11955431 DOI: 10.1016/S0092-8674(02)00672-4
Date:
14-Aug-01     Release date:   18-Apr-02    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P17927  (CR1_HUMAN) -  Complement receptor type 1 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		2039 a.a.
136 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 

 
DOI no: 10.1016/S0092-8674(02)00672-4 Cell 108:769-780 (2002)
PubMed id: 11955431  
 
 
Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor.
B.O.Smith, R.L.Mallin, M.Krych-Goldberg, X.Wang, R.E.Hauhart, K.Bromek, D.Uhrin, J.P.Atkinson, P.N.Barlow.
 
  ABSTRACT  
 
Complement receptor type 1 (CR1 or CD35) is a multiple modular protein that mediates the immune adherence phenomenon, a fundamental event for destroying microbes and initiating an immunological response. It fulfills this role through binding C3b/C4b-opsonized foreign antigens. The structure of the principal C3b/C4b binding site (residues 901-1095) of CR1 is reported, revealing three complement control protein modules (modules 15-17) in an extended head-to-tail arrangement with flexibility at the 16-17 junction. Structure-guided mutagenesis identified a positively charged surface region on module 15 that is critical for C4b binding. This patch, together with basic side chains of module 16 exposed on the same face of CR1, is required for C3b binding. These studies reveal the initial structural details of one of the first receptor-ligand interactions to be identified in immunobiology.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Mutations Mapped onto Surface of Site 2Left: surface of CR1 vert, similar 15–17 using color scheme (red, 15; cyan, 16; blue, 17), except where mutagenesis yielded no significant loss of C3b (iC3) binding or C4b binding (black), some loss of C3b (iC3) binding (aa 937, 1053) or C4b binding (aa 927, 929, 1046) (yellow), or major loss of C3b and/or C4b binding (white). Single asterisk indicates residues that, when incorporated at their equivalent positions in site 1 (i.e., D109N, N29K, and T14K), caused gain of C3b binding. Double asterisk indicates two residues (Y27S/G79D) that confer C3b binding activity when simultaneously inserted at their equivalent positions in site 1.Right: same features but rotated (about vertical axis) by 180°. 		Figure 5.
Figure 5. Ligand Binding by Charge-Reverse Mutants in Site 2(A) iC3-Sepharose(B) C4b-SepharoseOne representative measurement of two-to-four is shown by each data point. In the case of C4b binding, mutants had binding values of ≤6% compared to the parent fragment. Results are expressed as a percentage of CR1 derivative bound to iC3-S or C4b-S of that initially offered to the Sepharose.
 
  The above figures are reprinted by permission from Cell Press: Cell (2002, 108, 769-780) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20796027 A.Láng, K.Szilágyi, B.Major, P.Gál, P.Závodszky, and A.Perczel (2010).
Intermodule cooperativity in the structure and dynamics of consecutive complement control modules in human C1r: structural biology.
  FEBS J, 277, 3986-3998.  
20149185 S.Miyagawa, A.Yamamoto, K.Matsunami, D.Wang, Y.Takama, T.Ueno, M.Okabe, H.Nagashima, and M.Fukuzawa (2010).
Complement regulation in the GalT KO era.
  Xenotransplantation, 17, 11-25.  
20646210 Y.Congbin, L.Aibin, Y.Congli, X.Juan, B.Lanjun, Z.Weiping, Y.Zhibiao, and H.Xiuguo (2010).
Overexpression of complement receptor type I (CR1, CD35) on erythrocytes in patients with hemoplasma infection.
  Microbiol Immunol, 54, 460-465.  
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.  
19237749 V.Krishnan, Y.Xu, K.Macon, J.E.Volanakis, and S.V.Narayana (2009).
The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation.
  Acta Crystallogr D Biol Crystallogr, 65, 266-274.
PDB code: 3erb
17467802 D.J.Birmingham, F.Irshaid, K.F.Gavit, H.N.Nagaraja, C.Y.Yu, B.H.Rovin, and L.A.Hebert (2007).
A polymorphism in the type one complement receptor (CR1) involves an additional cysteine within the C3b/C4b binding domain that inhibits ligand binding.
  Mol Immunol, 44, 3510-3516.  
17395591 L.Kuttner-Kondo, D.E.Hourcade, V.E.Anderson, N.Muqim, L.Mitchell, D.C.Soares, P.N.Barlow, and M.E.Medof (2007).
Structure-based mapping of DAF active site residues that accelerate the decay of C3 convertases.
  J Biol Chem, 282, 18552-18562.  
17590164 M.van Lookeren Campagne, C.Wiesmann, and E.J.Brown (2007).
Macrophage complement receptors and pathogen clearance.
  Cell Microbiol, 9, 2095-2102.  
17850488 R.Roozendaal, and M.C.Carroll (2007).
Complement receptors CD21 and CD35 in humoral immunity.
  Immunol Rev, 219, 157-166.  
17051152 A.Abdul Ajees, K.Gunasekaran, J.E.Volanakis, S.V.Narayana, G.J.Kotwal, and H.M.Murthy (2006).
The structure of complement C3b provides insights into complement activation and regulation.
  Nature, 444, 221-225.
PDB code: 2hr0
16533809 A.P.Herbert, D.Uhrín, M.Lyon, M.K.Pangburn, and P.N.Barlow (2006).
Disease-associated sequence variations congregate in a polyanion recognition patch on human factor H revealed in three-dimensional structure.
  J Biol Chem, 281, 16512-16520.
PDB code: 2bzm
16330538 H.T.Jenkins, L.Mark, G.Ball, J.Persson, G.Lindahl, D.Uhrin, A.M.Blom, and P.N.Barlow (2006).
Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor.
  J Biol Chem, 281, 3690-3697.
PDB code: 2a55
16473914 L.Zhang, and D.Morikis (2006).
Immunophysical properties and prediction of activities for vaccinia virus complement control protein and smallpox inhibitor of complement enzymes using molecular dynamics and electrostatics.
  Biophys J, 90, 3106-3119.  
15660833 A.Mqadmi, Y.Abdullah, and K.Yazdanbakhsh (2005).
Characterization of complement receptor 1 domains for prevention of complement-mediated red cell destruction.
  Transfusion, 45, 234-244.  
16046396 A.Sjöberg, P.Onnerfjord, M.Mörgelin, D.Heinegård, and A.M.Blom (2005).
The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q.
  J Biol Chem, 280, 32301-32308.  
15781579 I.Del Conde, M.A.Crúz, H.Zhang, J.A.López, and V.Afshar-Kharghan (2005).
Platelet activation leads to activation and propagation of the complement system.
  J Exp Med, 201, 871-879.  
15096630 J.M.O'Leary, K.Bromek, G.M.Black, S.Uhrinova, C.Schmitz, X.Wang, M.Krych, J.P.Atkinson, D.Uhrin, and P.N.Barlow (2004).
Backbone dynamics of complement control protein (CCP) modules reveals mobility in binding surfaces.
  Protein Sci, 13, 1238-1250.
PDB code: 1ppq
15304516 L.Mark, W.H.Lee, O.B.Spiller, D.Proctor, D.J.Blackbourn, B.O.Villoutreix, and A.M.Blom (2004).
The Kaposi's sarcoma-associated herpesvirus complement control protein mimics human molecular mechanisms for inhibition of the complement system.
  J Biol Chem, 279, 45093-45101.  
15304491 S.Blein, R.Ginham, D.Uhrin, B.O.Smith, D.C.Soares, S.Veltel, R.A.McIlhinney, J.H.White, and P.N.Barlow (2004).
Structural analysis of the complement control protein (CCP) modules of GABA(B) receptor 1a: only one of the two CCP modules is compactly folded.
  J Biol Chem, 279, 48292-48306.
PDB codes: 1srz 1ss2
15178763 V.K.Ganesh, S.A.Smith, G.J.Kotwal, and K.H.Murthy (2004).
Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation.
  Proc Natl Acad Sci U S A, 101, 8924-8929.
PDB code: 1rid
12672958 S.Uhrinova, F.Lin, G.Ball, K.Bromek, D.Uhrin, M.E.Medof, and P.N.Barlow (2003).
Solution structure of a functionally active fragment of decay-accelerating factor.
  Proc Natl Acad Sci U S A, 100, 4718-4723.
PDB code: 1nwv
12122212 A.E.Prota, D.R.Sage, T.Stehle, and J.D.Fingeroth (2002).
The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding.
  Proc Natl Acad Sci U S A, 99, 10641-10646.
PDB code: 1ly2
12421687 M.Krych-Goldberg, J.M.Moulds, and J.P.Atkinson (2002).
Human complement receptor type 1 (CR1) binds to a major malarial adhesin.
  Trends Mol Med, 8, 531-537.  
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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