PDBsum entry 3dsf

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Immune system PDB id
Protein chains
213 a.a.
216 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of anti-osteopontin antibody 23c3 in compl w43a mutated epitope peptide
Structure: Fab fragment of anti-osteopontin antibody 23c3, l chain. Chain: l. Fab fragment of anti-osteopontin antibody 23c3, h chain. Chain: h. A peptide from osteopontin. Chain: p. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Tissue: ascites. Synthetic: yes. Other_details: the peptide vatalnpdpsqk is synthesized at s hd bioscience company
2.80Å     R-factor:   0.244     R-free:   0.297
Authors: J.Du,C.Zhong,H.Yang,J.Ding
Key ref:
J.Du et al. (2008). Molecular basis of recognition of human osteopontin by 23C3, a potential therapeutic antibody for treatment of rheumatoid arthritis. J Mol Biol, 382, 835-842. PubMed id: 18694758 DOI: 10.1016/j.jmb.2008.07.075
12-Jul-08     Release date:   14-Oct-08    
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Protein chain
No UniProt id for this chain
Struc: 213 a.a.
Protein chain
No UniProt id for this chain
Struc: 216 a.a.
Key:    Secondary structure  CATH domain


DOI no: 10.1016/j.jmb.2008.07.075 J Mol Biol 382:835-842 (2008)
PubMed id: 18694758  
Molecular basis of recognition of human osteopontin by 23C3, a potential therapeutic antibody for treatment of rheumatoid arthritis.
J.Du, S.Hou, C.Zhong, Z.Lai, H.Yang, J.Dai, D.Zhang, H.Wang, Y.Guo, J.Ding.
Osteopontin plays an important role in the development and perpetuation of rheumatoid arthritis (RA). Antibodies targeting osteopontin have shown promising therapeutic benefits against this disease. We have previously reported a novel anti-RA monoclonal antibody, namely, 23C3, and shown it capable of alleviating the symptoms of RA in a murine collagen-induced arthritis model, restoring the cytokine production profile in joint tissues, and reducing T-cell recall responses to collagen type II. We describe here the crystal structure of 23C3 in complex with its epitope peptide. Analyses of the complex structure reveal the molecular mechanism of osteopontin recognition by 23C3. The peptide folds into two tandem beta-turns, and two key residues of the peptide are identified to be critical for the recognition by 23C3: TrpP43 is deeply embedded into a hydrophobic pocket formed by AlaL34, TyrL36, LeuL46, TyrL49, PheL91, and MetH102 and therefore has extensive hydrophobic interactions with 23C3, while AspP47 has a network of hydrophilic interactions with residues ArgH50, ArgH52, SerH53, and AsnH56 of the antibody. Besides the complementarity-determining region loops, the framework region L2 of 23C3 is also shown to interact with the epitope peptide, which is not common in the antibody-antigen interactions and thus could be exploited in the engineering of 23C3. These results not only provide valuable information for further improvement of 23C3 such as chimerization or humanization for its therapeutic application, but also reveal the features of this specific epitope of osteopontin that may be useful for the development of new antibody drugs against RA.
  Selected figure(s)  
Figure 1.
Fig. 1. Overall structure of the 23C3 Fab–epitope peptide complex. (a) Stereoview of the overall structure of the 23C3 Fab–epitope peptide complex. The 23C3 Fab light chain is colored yellow, the heavy chain is cyan, and the bound peptide is purple. The sugar chain is shown with a ball-and-stick model. (b) A stereo view representation of SIGMAA-weighted 2F[o] − F[c] map (1σ contour level) for the bound epitope peptide. The peptide is shown with a ball-and-stick model.
Figure 2.
Fig. 2. The interactions between the 23C3 Fab and the bound peptide. (a) An enlarged view of the interface surface. The peptide is bound at a pocket formed mainly by CDRs and interacts with CDRs L1, L3, H1, H2, and H3 and FWR L2. The Fab CDR L1 is colored lemon; L2, salmon; L3, cyan; H1, orange; H2, pink; H3, brown; FWR L2, olive; and other FWRs, silver. The peptide is colored purple. (b) A stereo view showing the hydrogen bonds between residues of the 23C3 Fab and residues of the epitope peptide. The color coding is the same as above. The residues that participate in the hydrogen-bonding interactions are shown with ball-and-stick models. (c) An electrostatic potential surface of the 23C3 Fab at the interface. The Fab accommodates the peptide with great structural and chemical complementarity. (d) The extensive hydrophobic interactions between the Fab and the key residue TrpP43 of the epitope peptide. Residues AlaL34 of CDR L1, PheL91 of CDR L3, MetH102 of CDR H3, and TyrL36, LeuL46, and TyrL49 of FWR L2 form a deep hydrophobic pocket to accommodate TrpP43 of the peptide. (e) The hydrophilic recognition of AspP47 by the Fab. AspP47 makes hydrogen-bonding interactions with SerH53, AsnH56, and ArgH52. It also forms electrostatic interactions with residues ArgH50 and ArgH52 of CDR H2. The color coding is the same as in (a).
  The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 382, 835-842) copyright 2008.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19603104 L.Bazzichi, L.Ghiadoni, A.Rossi, M.Bernardini, M.Lanza, F.De Feo, C.Giacomelli, I.Mencaroni, K.Raimo, M.Rossi, A.M.Mazzone, S.Taddei, and S.Bombardieri (2009).
Osteopontin is associated with increased arterial stiffness in rheumatoid arthritis.
  Mol Med, 15, 402-406.  
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