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PDBsum entry 2exp

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protein Protein-protein interface(s) links
Immune system PDB id
2exp
Jmol
Contents
Protein chains
109 a.a.
115 a.a.
16 a.a.
Theoretical model
PDB id:
2exp
Name: Immune system
Title: A complex of monoclonal antibody 806 with an egfr peptide (model 3)
Structure: Light chain from fv fragment of monoclonal antibody 806. Chain: l. Heavy chain from fv fragment of monoclonal antibody 806. Chain: h. Epidermal growth factor receptor. Chain: a. Synonym: receptor tyrosine-protein kinase erbb-1.
Source: Mus musculus. Mouse. Homo sapiens. Human
Authors: A.Sivasubramanian,G.Chao,H.M.Pressler,K.D.Wittrup,J.J.Gray
Key ref:
A.Sivasubramanian et al. (2006). Structural Model of the mAb 806-EGFR Complex Using Computational Docking followed by Computational and Experimental Mutagenesis. Structure, 14, 401-414. PubMed id: 16531225 DOI: 10.1016/j.str.2005.11.022
Date:
08-Nov-05     Release date:   04-Apr-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q7TS98  (Q7TS98_MOUSE) -  Anti-colorectal carcinoma light chain
Seq:
Struc:
236 a.a.
109 a.a.*
Protein chain
Pfam   ArchSchema ?
P18532  (HVM61_MOUSE) -  Ig heavy chain V region 1B43
Seq:
Struc:
116 a.a.
115 a.a.*
Protein chain
Pfam   ArchSchema ?
P00533  (EGFR_HUMAN) -  Epidermal growth factor receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1210 a.a.
16 a.a.
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 40 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.2.7.1.112  - Transferred entry: 2.7.10.1 and 2.7.10.2.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate

+ a
=
+
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/j.str.2005.11.022 Structure 14:401-414 (2006)
PubMed id: 16531225  
 
 
Structural Model of the mAb 806-EGFR Complex Using Computational Docking followed by Computational and Experimental Mutagenesis.
A.Sivasubramanian, G.Chao, H.M.Pressler, K.D.Wittrup, J.J.Gray.
 
  ABSTRACT  
 
In this work, we combined computational protein-protein docking with computational and experimental mutagenesis to predict the structure of the complex formed by monoclonal antibody 806 (mAb 806) and the epidermal growth factor receptor (EGFR). We docked mAb 806, an antitumor antibody, to its epitope of EGFR residues 287-302. Potential mAb 806-EGFR orientations were generated, and computational mutagenesis was used to filter them according to their agreement with experimental mutagenesis data. Further computational mutagenesis suggested additional mutations, which were tested to arrive at a final structure that was most consistent with experimental mutagenesis data. We propose that this is the EGFR-mAb 806 structure, in which mAb 806 binds to an untethered form of the receptor, consistent with published experimental results. The steric hindrance created by the antibody near the EGFR dimer interface interferes with receptor dimerization, and we postulate this as the structural origin for the antitumor effect of mAb 806.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Proposed Structure for the mAb 806-EGFR Complex
(A) Proposed structure for the mAb 806-EGFR complex, created by structurally aligning model 3 with the hypothetical extended monomer conformation. The coloring scheme is identical to that in Figure 5.
(B) Interface interactions: EGFR residue E293 forms a hydrogen bond with CDR H2 side chain Y50 and makes several hydrophobic contacts, mostly with residues in the mAb 806 H2 loop.
(C) EGFR residue D297 is well packed in a pocket of residues from the mAb 806 L2, L3, and H3 CDRs.
 
  The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 401-414) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20462859 F.Lauck, C.A.Smith, G.F.Friedland, E.L.Humphris, and T.Kortemme (2010).
RosettaBackrub--a web server for flexible backbone protein structure modeling and design.
  Nucleic Acids Res, 38, W569-W575.  
20235548 K.W.Kaufmann, G.H.Lemmon, S.L.Deluca, J.H.Sheehan, and J.Meiler (2010).
Practically useful: what the Rosetta protein modeling suite can do for you.
  Biochemistry, 49, 2987-2998.  
19458157 A.Sircar, E.T.Kim, and J.J.Gray (2009).
RosettaAntibody: antibody variable region homology modeling server.
  Nucleic Acids Res, 37, W474-W479.  
19062174 A.Sivasubramanian, A.Sircar, S.Chaudhury, and J.J.Gray (2009).
Toward high-resolution homology modeling of antibody Fv regions and application to antibody-antigen docking.
  Proteins, 74, 497-514.  
19066995 B.Sharma, and M.K.Jaiswal (2009).
EGF domain II of protein Pb28 from Plasmodium berghei interacts with monoclonal transmission blocking antibody 13.1.
  J Mol Model, 15, 369-382.  
18992239 K.R.Schmitz, and K.M.Ferguson (2009).
Interaction of antibodies with ErbB receptor extracellular regions.
  Exp Cell Res, 315, 659-670.  
19289842 T.P.Garrett, A.W.Burgess, H.K.Gan, R.B.Luwor, G.Cartwright, F.Walker, S.G.Orchard, A.H.Clayton, E.C.Nice, J.Rothacker, B.Catimel, W.K.Cavenee, L.J.Old, E.Stockert, G.Ritter, T.E.Adams, P.A.Hoyne, D.Wittrup, G.Chao, J.R.Cochran, C.Luo, M.Lou, T.Huyton, Y.Xu, W.D.Fairlie, S.Yao, A.M.Scott, and T.G.Johns (2009).
Antibodies specifically targeting a locally misfolded region of tumor associated EGFR.
  Proc Natl Acad Sci U S A, 106, 5082-5087.
PDB codes: 3g5v 3g5x 3g5y 3g5z
17671962 A.Sivasubramanian, J.A.Maynard, and J.J.Gray (2008).
Modeling the structure of mAb 14B7 bound to the anthrax protective antigen.
  Proteins, 70, 218-230.  
18318657 F.Alber, F.Förster, D.Korkin, M.Topf, and A.Sali (2008).
Integrating diverse data for structure determination of macromolecular assemblies.
  Annu Rev Biochem, 77, 443-477.  
18640688 S.Chaudhury, and J.J.Gray (2008).
Conformer selection and induced fit in flexible backbone protein-protein docking using computational and NMR ensembles.
  J Mol Biol, 381, 1068-1087.  
18442991 S.Lyskov, and J.J.Gray (2008).
The RosettaDock server for local protein-protein docking.
  Nucleic Acids Res, 36, W233-W238.  
17877819 B.A.McKinney, N.L.Kallewaard, J.E.Crowe, and J.Meiler (2007).
Using the natural evolution of a rotavirus-specific human monoclonal antibody to predict the complex topography of a viral antigenic site.
  Immunome Res, 3, 8.  
18075576 C.V.Robinson, A.Sali, and W.Baumeister (2007).
The molecular sociology of the cell.
  Nature, 450, 973-982.  
17894347 S.Chaudhury, A.Sircar, A.Sivasubramanian, M.Berrondo, and J.J.Gray (2007).
Incorporating biochemical information and backbone flexibility in RosettaDock for CAPRI rounds 6-12.
  Proteins, 69, 793-800.  
17723181 Z.Zhu (2007).
Targeted cancer therapies based on antibodies directed against epidermal growth factor receptor: status and perspectives.
  Acta Pharmacol Sin, 28, 1476-1493.  
16546374 J.J.Gray (2006).
High-resolution protein-protein docking.
  Curr Opin Struct Biol, 16, 183-193.  
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 codes are shown on the right.