PDBsum entry 1adq

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protein Protein-protein interface(s) links
Complex (immunoglobulin/autoantigen) PDB id
Protein chains
206 a.a. *
213 a.a. *
225 a.a. *
* Residue conservation analysis
PDB id:
Name: Complex (immunoglobulin/autoantigen)
Title: Crystal structure of a human igm rheumatoid factor fab in complex with its autoantigen igg fc
Structure: Igg4 rea fc. Chain: a. Fragment: fc. Igm-lambda rf-an fab (light chain). Chain: l. Fragment: fab. Igm-lambda rf-an fab (heavy chain). Chain: h. Fragment: fab
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: b-lymphocyte. Cellular_location: extracellular. Other_details: isolated from the sera of patients with multiple myeloma. Cell_line: rf-an. Other_details: rf-an cell line was prepared from
Biol. unit: Monomer (from PDB file)
3.15Å     R-factor:   0.225     R-free:   0.289
Authors: A.L.Corper,M.J.Taussig,B.J.Sutton
Key ref: A.L.Corper et al. (1997). Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction. Nat Struct Biol, 4, 374-381. PubMed id: 9145108
18-Feb-97     Release date:   16-Sep-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01861  (IGHG4_HUMAN) -  Ig gamma-4 chain C region
327 a.a.
206 a.a.*
Protein chain
No UniProt id for this chain
Struc: 213 a.a.
Protein chain
No UniProt id for this chain
Struc: 225 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)


Nat Struct Biol 4:374-381 (1997)
PubMed id: 9145108  
Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction.
A.L.Corper, M.K.Sohi, V.R.Bonagura, M.Steinitz, R.Jefferis, A.Feinstein, D.Beale, M.J.Taussig, B.J.Sutton.
Rheumatoid factors are the characteristic autoantibodies of rheumatoid arthritis, which bind to the Fc regions of IgG molecules. Here we report the crystal structure of the Fab fragment of a patient-derived IgM rheumatoid factor (RF-AN) complexed with human IgG4 Fc, at 3.2 A resolution. This is the first structure of an autoantibody-autoantigen complex. The epitope recognised in IgG Fc includes the C gamma 2/C gamma 3 cleft region, and overlaps the binding sites of bacterial Fc-binding proteins. The antibody residues involved in autorecognition are all located at the edge of the conventional combining site surface, leaving much of the latter available, potentially, for recognition of a different antigen. Since an important contact residue is somatic mutation, the structure implicates antigen-driven selection, following somatic mutation of germline genes, in the production of pathogenic rheumatoid factors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21191378 Y.Zheng, H.Scheerens, J.C.Davis, R.Deng, S.K.Fischer, C.Woods, P.J.Fielder, and E.G.Stefanich (2011).
Translational Pharmacokinetics and Pharmacodynamics of an FcRn-Variant Anti-CD4 Monoclonal Antibody From Preclinical Model to Phase I Study.
  Clin Pharmacol Ther, 89, 283-290.  
21031477 A.S.Kamalanathan, C.Goulvestre, B.Weill, and M.A.Vijayalakshmi (2010).
Proteolysis activity of IgM antibodies from rheumatoid arthritis patients' sera: evidence of atypical catalytic site.
  J Mol Recognit, 23, 577-582.  
20848524 R.K.Weersma, J.B.Crusius, R.L.Roberts, B.P.Koeleman, R.Palomino-Morales, S.Wolfkamp, J.E.Hollis-Moffatt, E.A.Festen, S.Meisneris, R.Heijmans, C.L.Noble, R.B.Gearry, M.L.Barclay, M.Gómez-Garcia, M.A.Lopez-Nevot, A.Nieto, L.Rodrigo, T.R.Radstake, A.A.van Bodegraven, C.Wijmenga, T.R.Merriman, P.C.Stokkers, A.S.Peña, J.Martín, and B.Z.Alizadeh (2010).
Association of FcgR2a, but not FcgR3a, with inflammatory bowel diseases across three Caucasian populations.
  Inflamm Bowel Dis, 16, 2080-2089.  
19165723 H.Pan, K.Chen, L.Chu, F.Kinderman, I.Apostol, and G.Huang (2009).
Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn.
  Protein Sci, 18, 424-433.  
18957574 S.Bonetto, L.Spadola, A.G.Buchanan, L.Jermutus, and J.Lund (2009).
Identification of cyclic peptides able to mimic the functional epitope of IgG1-Fc for human Fc gammaRI.
  FASEB J, 23, 575-585.  
18420815 A.H.Keeble, Z.Khan, A.Forster, and L.C.James (2008).
TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved.
  Proc Natl Acad Sci U S A, 105, 6045-6050.
PDB codes: 2vok 2vol 3zo0
18216124 E.R.Sprague, H.Reinhard, E.J.Cheung, A.H.Farley, R.D.Trujillo, H.Hengel, and P.J.Bjorkman (2008).
The human cytomegalovirus Fc receptor gp68 binds the Fc CH2-CH3 interface of immunoglobulin G.
  J Virol, 82, 3490-3499.  
18064051 F.Nimmerjahn, and J.V.Ravetch (2008).
Fcgamma receptors as regulators of immune responses.
  Nat Rev Immunol, 8, 34-47.  
18379088 Y.C.Liu, Z.Y.Yang, J.Du, X.J.Yao, R.X.Lei, X.D.Zheng, J.N.Liu, H.S.Hu, and H.Li (2008).
Study on the interactions of kaempferol and quercetin with intravenous immunoglobulin by fluorescence quenching, fourier transformation infrared spectroscopy and circular dichroism spectroscopy.
  Chem Pharm Bull (Tokyo), 56, 443-451.  
17703228 D.C.Roopenian, and S.Akilesh (2007).
FcRn: the neonatal Fc receptor comes of age.
  Nat Rev Immunol, 7, 715-725.  
17400754 L.C.James, A.H.Keeble, Z.Khan, D.A.Rhodes, and J.Trowsdale (2007).
Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function.
  Proc Natl Acad Sci U S A, 104, 6200-6205.
PDB code: 2iwg
17848512 P.A.Ramsland, N.Willoughby, H.M.Trist, W.Farrugia, P.M.Hogarth, J.D.Fraser, and B.D.Wines (2007).
Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1.
  Proc Natl Acad Sci U S A, 104, 15051-15056.
PDB code: 2qej
16646632 E.R.Sprague, C.Wang, D.Baker, and P.J.Bjorkman (2006).
Crystal structure of the HSV-1 Fc receptor bound to Fc reveals a mechanism for antibody bipolar bridging.
  PLoS Biol, 4, e148.
PDB codes: 2giy 2gj7
16617326 V.De Re, D.Sansonno, M.P.Simula, L.Caggiari, D.Gasparotto, M.Fabris, F.A.Tucci, V.Racanelli, R.Talamini, M.Campagnolo, S.Geremia, F.Dammacco, and S.De Vita (2006).
HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations.
  Leukemia, 20, 1145-1154.  
15903235 R.Jefferis (2005).
Glycosylation of recombinant antibody therapeutics.
  Biotechnol Prog, 21, 11-16.  
14734541 E.R.Sprague, W.L.Martin, and P.J.Bjorkman (2004).
pH dependence and stoichiometry of binding to the Fc region of IgG by the herpes simplex virus Fc receptor gE-gI.
  J Biol Chem, 279, 14184-14193.  
15466462 J.Agniswamy, B.Lei, J.M.Musser, and P.D.Sun (2004).
Insight of host immune evasion mediated by two variants of group a Streptococcus Mac protein.
  J Biol Chem, 279, 52789-52796.  
15103252 T.Dörner, K.Egerer, E.Feist, and G.R.Burmester (2004).
Rheumatoid factor revisited.
  Curr Opin Rheumatol, 16, 246-253.  
12768205 A.B.Herr, E.R.Ballister, and P.J.Bjorkman (2003).
Insights into IgA-mediated immune responses from the crystal structures of human FcalphaRI and its complex with IgA1-Fc.
  Nature, 423, 614-620.
PDB codes: 1ovz 1ow0
12757620 B.D.Wines, A.Gavin, M.S.Powell, M.Steinitz, R.R.Buchanan, and P.Mark Hogarth (2003).
Soluble FcgammaRIIa inhibits rheumatoid factor binding to immune complexes.
  Immunology, 109, 246-254.  
12610298 L.C.James, P.Roversi, and D.S.Tawfik (2003).
Antibody multispecificity mediated by conformational diversity.
  Science, 299, 1362-1367.
PDB codes: 1oaq 1oar 1oau 1oax 1oay 1oaz 1ocw
12072529 C.N.Scanlan, R.Pantophlet, M.R.Wormald, E.Ollmann Saphire, R.Stanfield, I.A.Wilson, H.Katinger, R.A.Dwek, P.M.Rudd, and D.R.Burton (2002).
The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1-->2 mannose residues on the outer face of gp120.
  J Virol, 76, 7306-7321.  
11849310 R.C.Aalberse, and J.Schuurman (2002).
IgG4 breaking the rules.
  Immunology, 105, 9.  
11349025 A.Loukas, M.K.Jones, L.T.King, P.J.Brindley, and D.P.McManus (2001).
Receptor for Fc on the surfaces of schistosomes.
  Infect Immun, 69, 3646-3651.  
12186495 E.Hendry, G.Taylor, F.Grennan-Jones, A.Sullivan, N.Liddy, J.Godfrey, N.Hayakawa, M.Powell, J.Sanders, J.Furmaniak, and B.R.Smith (2001).
X-ray crystal structure of a monoclonal antibody that binds to a major autoantigenic epitope on thyroid peroxidase.
  Thyroid, 11, 1091-1099.  
11336709 W.L.Martin, A.P.West, L.Gan, and P.J.Bjorkman (2001).
Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding.
  Mol Cell, 7, 867-877.
PDB codes: 1i1a 1i1c
10903952 E.J.Sundberg, and R.A.Mariuzza (2000).
Luxury accommodations: the expanding role of structural plasticity in protein-protein interactions.
  Structure, 8, R137-R142.  
11094437 E.Peen, and R.C.Williams (2000).
What you should know about PR3-ANCA. Structural aspects of antibodies to proteinase 3 (PR3).
  Arthritis Res, 2, 255-259.  
10469243 D.G.Williams, S.P.Moyes, and R.A.Mageed (1999).
Rheumatoid factor isotype switch and somatic mutation variants within rheumatoid arthritis synovium.
  Immunology, 98, 123-136.  
10607675 I.A.Wilson, and L.K.Jolliffe (1999).
The structure, organization, activation and plasticity of the erythropoietin receptor.
  Curr Opin Struct Biol, 9, 696-704.  
10425673 M.R.Wormald, and R.A.Dwek (1999).
Glycoproteins: glycan presentation and protein-fold stability.
  Structure, 7, R155-R160.  
10446868 M.Watson, P.M.Rudd, M.Bland, R.A.Dwek, and J.S.Axford (1999).
Sugar printing rheumatic diseases: a potential method for disease differentiation using immunoglobulin G oligosaccharides.
  Arthritis Rheum, 42, 1682-1690.  
  10520896 M.Zhang, and A.Davidson (1999).
A rheumatoid factor specific mimotope identified by a peptide display library.
  Autoimmunity, 30, 131-142.  
10440996 P.A.Ramsland, B.F.Movafagh, M.Reichlin, and A.B.Edmundson (1999).
Interference of rheumatoid factor activity by aspartame, a dipeptide methyl ester.
  J Mol Recognit, 12, 249-257.  
10066744 T.L.Chapman, I.You, I.M.Joseph, P.J.Bjorkman, S.L.Morrison, and M.Raghavan (1999).
Characterization of the interaction between the herpes simplex virus type I Fc receptor and immunoglobulin G.
  J Biol Chem, 274, 6911-6919.  
9523114 I.A.Wilson, and P.J.Bjorkman (1998).
Unusual MHC-like molecules: CD1, Fc receptor, the hemochromatosis gene product, and viral homologs.
  Curr Opin Immunol, 10, 67-73.  
9700500 L.J.Harris, S.B.Larson, E.Skaletsky, and A.McPherson (1998).
Comparison of the conformations of two intact monoclonal antibodies with hinges.
  Immunol Rev, 163, 35-43.  
  9623502 P.J.Delves (1998).
The role of glycosylation in autoimmune disease.
  Autoimmunity, 27, 239-253.  
9700502 R.Jefferis, J.Lund, and J.D.Pound (1998).
IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.
  Immunol Rev, 163, 59-76.  
  9573224 Z.Che, N.H.Olson, D.Leippe, W.M.Lee, A.G.Mosser, R.R.Rueckert, T.S.Baker, and T.J.Smith (1998).
Antibody-mediated neutralization of human rhinovirus 14 explored by means of cryoelectron microscopy and X-ray crystallography of virus-Fab complexes.
  J Virol, 72, 4610-4622.
PDB code: 1a6t
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