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PDBsum entry 2dts
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Immune system PDB id
2dts

 

 

 

 

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Contents
Protein chain
211 a.a. *
Ligands
NAG-NAG-BMA-MAN-
NAG-MAN
NAG-NAG-BMA-MAN-
NAG-MAN-NAG
Waters ×108
* Residue conservation analysis
PDB id:
2dts
Name: Immune system
Title: Crystal structure of the defucosylated fc fragment from human immunoglobulin g1
Structure: Ig gamma-1 chain c region. Chain: a, b. Fragment: fc fragment. Synonym: immunoglobulin g1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ighg1. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: cho.
Resolution:
2.20Å     R-factor:   0.195     R-free:   0.251
Authors: S.Matsumiya,Y.Yamaguchi,J.Saito,M.Nagano,H.Sasakawa,S.Otaki,M.Satoh, K.Shitara,K.Kato
Key ref:
S.Matsumiya et al. (2007). Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J Mol Biol, 368, 767-779. PubMed id: 17368483 DOI: 10.1016/j.jmb.2007.02.034
Date:
14-Jul-06     Release date:   13-Mar-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens
Seq:
Struc: 		399 a.a.
211 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/j.jmb.2007.02.034 J Mol Biol 368:767-779 (2007)
PubMed id: 17368483  
 
 
Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1.
S.Matsumiya, Y.Yamaguchi, J.Saito, M.Nagano, H.Sasakawa, S.Otaki, M.Satoh, K.Shitara, K.Kato.
 
  ABSTRACT  
 
Removal of the fucose residue from the oligosaccharides attached to Asn297 of human immunoglobulin G1 (IgG1) results in a significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to Fcgamma receptor IIIa. To provide structural insight into the mechanisms of affinity enhancement, we determined the crystal structure of the nonfucosylated Fc fragment and compared it with that of fucosylated Fc. The overall conformations of the fucosylated and nonfucosylated Fc fragments were similar except for hydration mode around Tyr296. Stable-isotope-assisted NMR analyses confirmed the similarity of the overall structures between fucosylated and nonfucosylated Fc fragments in solution. These data suggest that the glycoform-dependent ADCC enhancement is attributed to a subtle conformational alteration in a limited region of IgG1-Fc. Furthermore, the electron density maps revealed that the traces between Asp280 and Asn297 of our fucosylated and nonfucosylated Fc crystals were both different from that in previously reported isomorphous Fc crystals.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Environment around Tyr296. Possible hydrogen bonds are indicated by blue broken lines accompanied by interatomic distance (Å). (a) Chain A of Fuc (+). (b) Chain A of Fuc (−).
Figure 7.
Figure 7. Interface between the C′/E loop of Fc and FcγRIII. Intermolecular hydrogen bonds are shown by broken lines. (a) Fc (magenta)–FcγRIII (red) complex (hexagonal form, PDB ID: 1E4K). (b) Fc (blue)–FcγRIII (yellow) complex (orthorhombic form, PDB ID: 1T83).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 368, 767-779) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22460124 P.M.Hogarth, and G.A.Pietersz (2012).
Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond.
  Nat Rev Drug Discov, 11, 311-331.  
21481778 E.Karaca, and A.M.Bonvin (2011).
A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes.
  Structure, 19, 555-565.  
20665659 I.J.del Val, C.Kontoravdi, and J.M.Nagy (2010).
Towards the implementation of quality by design to the production of therapeutic monoclonal antibodies with desired glycosylation patterns.
  Biotechnol Prog, 26, 1505-1527.  
20414206 K.G.Smith, and M.R.Clatworthy (2010).
FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications.
  Nat Rev Immunol, 10, 328-343.  
21029072 Y.Machino, H.Ohta, E.Suzuki, S.Higurashi, T.Tezuka, H.Nagashima, J.Kohroki, and Y.Masuho (2010).
Effect of immunoglobulin G (IgG) interchain disulfide bond cleavage on efficacy of intravenous immunoglobulin for immune thrombocytopenic purpura (ITP).
  Clin Exp Immunol, 162, 415-424.  
  19920917 A.Natsume, R.Niwa, and M.Satoh (2009).
Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC.
  Drug Des Devel Ther, 3, 7.  
19265386 D.Houde, J.Arndt, W.Domeier, S.Berkowitz, and J.R.Engen (2009).
Characterization of IgG1 conformation and conformational dynamics by hydrogen/deuterium exchange mass spectrometry.
  Anal Chem, 81, 2644-2651.
PDB code: 3fzu
19122430 K.Shitara (2009).
Potelligent antibodies as next generation therapeutic antibodies.
  Yakugaku Zasshi, 129, 3-9.  
18952826 M.Shibata-Koyama, S.Iida, A.Okazaki, K.Mori, K.Kitajima-Miyama, S.Saitou, S.Kakita, Y.Kanda, K.Shitara, K.Kato, and M.Satoh (2009).
The N-linked oligosaccharide at Fc gamma RIIIa Asn-45: an inhibitory element for high Fc gamma RIIIa binding affinity to IgG glycoforms lacking core fucosylation.
  Glycobiology, 19, 126-134.  
  20065644 N.Yamane-Ohnuki, and M.Satoh (2009).
Production of therapeutic antibodies with controlled fucosylation.
  MAbs, 1, 230-236.  
19247305 R.Jefferis (2009).
Glycosylation as a strategy to improve antibody-based therapeutics.
  Nat Rev Drug Discov, 8, 226-234.  
18064051 F.Nimmerjahn, and J.V.Ravetch (2008).
Fcgamma receptors as regulators of immune responses.
  Nat Rev Immunol, 8, 34-47.  
18566325 M.Peipp, J.J.Lammerts van Bueren, T.Schneider-Merck, W.W.Bleeker, M.Dechant, T.Beyer, R.Repp, P.H.van Berkel, T.Vink, J.G.van de Winkel, P.W.Parren, and T.Valerius (2008).
Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells.
  Blood, 112, 2390-2399.  
18931413 P.Prabakaran, B.K.Vu, J.Gan, Y.Feng, D.S.Dimitrov, and X.Ji (2008).
Structure of an isolated unglycosylated antibody C(H)2 domain.
  Acta Crystallogr D Biol Crystallogr, 64, 1062-1067.
PDB code: 3dj9
18602995 P.W.Parren, and J.G.van de Winkel (2008).
An integrated science-based approach to drug development.
  Curr Opin Immunol, 20, 426-430.  
18441054 S.Miyakawa, Y.Nomura, T.Sakamoto, Y.Yamaguchi, K.Kato, S.Yamazaki, and Y.Nakamura (2008).
Structural and molecular basis for hyperspecificity of RNA aptamer to human immunoglobulin G.
  RNA, 14, 1154-1163.  
18339626 T.M.Dillon, M.S.Ricci, C.Vezina, G.C.Flynn, Y.D.Liu, D.S.Rehder, M.Plant, B.Henkle, Y.Li, S.Deechongkit, B.Varnum, J.Wypych, A.Balland, and P.V.Bondarenko (2008).
Structural and functional characterization of disulfide isoforms of the human IgG2 subclass.
  J Biol Chem, 283, 16206-16215.  
18606225 T.S.Raju (2008).
Terminal sugars of Fc glycans influence antibody effector functions of IgGs.
  Curr Opin Immunol, 20, 471-478.  
18560159 V.Oganesyan, C.Gao, L.Shirinian, H.Wu, and W.F.Dall'Acqua (2008).
Structural characterization of a human Fc fragment engineered for lack of effector functions.
  Acta Crystallogr D Biol Crystallogr, 64, 700-704.
PDB code: 3c2s
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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