5WTT

Structure of the 093G9 Fab in complex with the epitope peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.225 

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This is version 1.1 of the entry. See complete history


Literature

Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9.

Zhong, C.Huo, R.Hu, K.Shen, J.Li, D.Li, N.Ding, J.

(2017) J Mol Recognit 30

  • DOI: https://doi.org/10.1002/jmr.2645
  • Primary Citation of Related Structures:  
    5WTT

  • PubMed Abstract: 

    CCN1, also named Cyr61 (cysteine-rich protein 61), is the first identified member of the CCN family that is composed of 6 secreted extracellular matrix-associated glycoproteins. CCN1 has been demonstrated to participate in pathogenesis of rheumatoid arthritis through various pathways. A monoclonal antibody, namely, 093G9, is effective to antagonize the effects of CCN1 and hence has potential therapeutic benefits against rheumatoid arthritis. Here, we show that the epitope recognized by 093G9 is mapped to residues 77 to 80 of CCN1, and a cyclic peptide encompassing residues 75 to 81 of CCN1 displays high binding affinity for 093G9. The crystal structure of the 093G9 Fab in complex with the cyclic peptide was determined at 2.7 Å resolution, which reveals the intensive interactions between CCN1 and 093G9. Particularly, residues Asn79 and Phe80 of CCN1 are inserted into cavities mainly formed by residues of complementarity-determining region loop L3 and framework region L2 and by residues of complementarity-determining region loops H2 and H3, respectively, which contribute most of the interactions and therefore are critical for the recognition by 093G9. Together, these findings not only identify the epitope of CCN1 for 093G9 but also reveal the molecular mechanism of recognition and binding of CCN1 by 093G9.


  • Organizational Affiliation

    National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chain of 093G9 FabA [auth H],
D [auth A]
241Mus musculusMutation(s): 0 
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Light chain of 093G9 FabB [auth L],
E [auth B]
239Homo sapiensMutation(s): 0 
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Epitope peptide of Cyr61C [auth P],
F [auth C]
8Homo sapiensMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.222 
  • R-Value Observed: 0.225 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.883α = 90
b = 214.437β = 92.81
c = 50.045γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data processing
PHENIXphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-12-20
    Type: Initial release
  • Version 1.1: 2019-01-02
    Changes: Data collection, Database references