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PDBsum entry 1e6o

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protein Protein-protein interface(s) links
Immunoglobulin PDB id
1e6o
Jmol
Contents
Protein chains
219 a.a. *
210 a.a. *
Waters ×237
* Residue conservation analysis
PDB id:
1e6o
Name: Immunoglobulin
Title: Crystal structure of fab13b5 against HIV-1 capsid protein p24
Structure: Immunoglobulin light chain. Chain: l. Fragment: light chain 1-210. Other_details: obtained by pepsin cleavage (fab'). Immunoglobulin heavy chain. Chain: h. Fragment: heavy chain 1-219. Other_details: obtained by pepsin cleavage (fab')
Source: Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090
Biol. unit: Hetero-Dimer (from PDB file)
Resolution:
1.8Å     R-factor:   0.225     R-free:   0.255
Authors: S.Monaco-Malbet,C.Berthet-Colominas,A.Novelli,N.Battai, N.Piga,F.Mallet,S.Cusack
Key ref:
S.Monaco-Malbet et al. (2000). Mutual conformational adaptations in antigen and antibody upon complex formation between an Fab and HIV-1 capsid protein p24. Structure, 8, 1069-1077. PubMed id: 11080628 DOI: 10.1016/S0969-2126(00)00507-4
Date:
21-Aug-00     Release date:   27-Nov-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 219 a.a.
Protein chain
No UniProt id for this chain
Struc: 210 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1016/S0969-2126(00)00507-4 Structure 8:1069-1077 (2000)
PubMed id: 11080628  
 
 
Mutual conformational adaptations in antigen and antibody upon complex formation between an Fab and HIV-1 capsid protein p24.
S.Monaco-Malbet, C.Berthet-Colominas, A.Novelli, N.Battaï, N.Piga, V.Cheynet, F.Mallet, S.Cusack.
 
  ABSTRACT  
 
BACKGROUND: Elucidating the structural basis of antigen-antibody recognition ideally requires a structural comparison of free and complexed components. To this end we have studied a mouse monoclonal antibody, denoted 13B5, raised against p24, the capsid protein of HIV-1. We have previously described the first crystal structure of intact p24 as visualized in the Fab13B5-p24 complex. Here we report the structure of the uncomplexed Fab13B5 at 1.8 A resolution and analyze the Fab-p24 interface and the conformational changes occurring upon complex formation. RESULTS: Fab13B5 recognizes a nearly continuous epitope comprising a helix-turn-helix motif in the C-terminal domain of p24. Only 4 complementarity-determining regions (CDRs) are in contact with p24 with most interactions being by the heavy chain. Comparison of the free and complexed Fab reveals that structural changes upon binding are localized to a few side chains of CDR-H1 and -H2 but involve a larger, concerted displacement of CDR-H3. Antigen binding is also associated with an 8 degrees relative rotation of the heavy and light chain variable regions. In p24, small conformational changes localized to the turn between the two helices comprising the epitope result from Fab binding. CONCLUSIONS: The relatively small area of contact between Fab13B5 and p24 may be related to the fact that the epitope is a continuous peptide rather than a more complex protein surface and correlates with a relatively low affinity of antigen and antibody. Despite this, a significant quaternary structural change occurs in the Fab upon complex formation, with additional smaller adaptations of both antigen and antibody.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Adaptation of the p24 Epitope upon Fab BindingThe C-terminal domain of p24 in the epitope region (H10-turn-H11) as in the Fab complex (red) is superposed on the isolated C-terminal domain of p24 (green; Protein Data Bank entry 1AM3, [19]), showing conformational differences at Pro-207

 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1069-1077) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21170360 W.S.Blair, C.Pickford, S.L.Irving, D.G.Brown, M.Anderson, R.Bazin, J.Cao, G.Ciaramella, J.Isaacson, L.Jackson, R.Hunt, A.Kjerrstrom, J.A.Nieman, A.K.Patick, M.Perros, A.D.Scott, K.Whitby, H.Wu, and S.L.Butler (2010).
HIV capsid is a tractable target for small molecule therapeutic intervention.
  PLoS Pathog, 6, e1001220.
PDB code: 2xde
  20140073 S.S.Negi, and W.Braun (2009).
Automated detection of conformational epitopes using phage display Peptide sequences.
  Bioinform Biol Insights, 3, 71-81.  
18193057 M.O.Lasaro, N.Tatsis, S.E.Hensley, J.C.Whitbeck, S.W.Lin, J.J.Rux, E.J.Wherry, G.H.Cohen, R.J.Eisenberg, and H.C.Ertl (2008).
Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responses.
  Nat Med, 14, 205-212.  
17442718 L.S.Larsen, M.Zhang, N.Beliakova-Bethell, V.Bilanchone, A.Lamsa, K.Nagashima, R.Najdi, K.Kosaka, V.Kovacevic, J.Cheng, P.Baldi, G.W.Hatfield, and S.Sandmeyer (2007).
Ty3 capsid mutations reveal early and late functions of the amino-terminal domain.
  J Virol, 81, 6957-6972.  
17252586 M.J.Bobeck, and G.D.Glick (2007).
Role of conformational dynamics in sequence-specific autoantibody*ssDNA recognition.
  Biopolymers, 85, 481-489.  
  17903253 S.Abdurahman, M.Youssefi, S.Höglund, and A.Vahlne (2007).
Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity.
  Retrovirology, 4, 69.  
  17371591 S.Abdurahman, S.Höglund, A.Höglund, and A.Vahlne (2007).
Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity.
  Retrovirology, 4, 19.  
16683021 C.J.Tsai, J.Zheng, and R.Nussinov (2006).
Designing a nanotube using naturally occurring protein building blocks.
  PLoS Comput Biol, 2, e42.  
15858274 G.H.Cohen, E.W.Silverton, E.A.Padlan, F.Dyda, J.A.Wibbenmeyer, R.C.Willson, and D.R.Davies (2005).
Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7 A resolution: comparison with results from isothermal titration calorimetry.
  Acta Crystallogr D Biol Crystallogr, 61, 628-633.
PDB code: 1yqv
15778960 M.Król, I.Roterman, B.Piekarska, L.Konieczny, J.Rybarska, B.Stopa, and P.Spólnik (2005).
Analysis of correlated domain motions in IgG light chain reveals possible mechanisms of immunological signal transduction.
  Proteins, 59, 545-554.  
14715087 W.R.Taylor, and J.P.Stoye (2004).
Consensus structural models for the amino terminal domain of the retrovirus restriction gene Fv1 and the murine leukaemia virus capsid proteins.
  BMC Struct Biol, 4, 1.  
11536361 C.Baysal, and A.R.Atilgan (2001).
Coordination topology and stability for the native and binding conformers of chymotrypsin inhibitor 2.
  Proteins, 45, 62-70.  
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.