spacer
spacer

PDBsum entry 3ifo

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Immune system PDB id
3ifo
Jmol
Contents
Protein chains
216 a.a. *
218 a.a. *
Ligands
ALA-GLU-PHE-ARG-
HIS-ASP
×2
Waters ×842
* Residue conservation analysis
PDB id:
3ifo
Name: Immune system
Title: X-ray structure of amyloid beta peptide:antibody (abeta1-7:1 complex
Structure: 10d5 fab antibody heavy chain. Chain: h, a. Engineered: yes. 10d5 fab antibody light chain. Chain: l, b. Engineered: yes. Amyloid beta a4 protein. Chain: p, q. Fragment: residues 672-678.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: cricetulus griseus. Expression_system_taxid: 10090. Expression_system_cell_line: cho cells. Expression_system_tissue: ovary. Synthetic: yes. Homo sapiens.
Resolution:
2.15Å     R-factor:   0.165     R-free:   0.218
Authors: W.I.Weis,H.Feinberg,G.S.Basi,D.Schenk
Key ref: G.S.Basi et al. (2010). Structural correlates of antibodies associated with acute reversal of amyloid beta-related behavioral deficits in a mouse model of Alzheimer disease. J Biol Chem, 285, 3417-3427. PubMed id: 19923222
Date:
24-Jul-09     Release date:   17-Nov-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 216 a.a.
Protein chains
No UniProt id for this chain
Struc: 218 a.a.
Key:    Secondary structure  CATH domain

 

 
J Biol Chem 285:3417-3427 (2010)
PubMed id: 19923222  
 
 
Structural correlates of antibodies associated with acute reversal of amyloid beta-related behavioral deficits in a mouse model of Alzheimer disease.
G.S.Basi, H.Feinberg, F.Oshidari, J.Anderson, R.Barbour, J.Baker, T.A.Comery, L.Diep, D.Gill, K.Johnson-Wood, A.Goel, K.Grantcharova, M.Lee, J.Li, A.Partridge, I.Griswold-Prenner, N.Piot, D.Walker, A.Widom, M.N.Pangalos, P.Seubert, J.S.Jacobsen, D.Schenk, W.I.Weis.
 
  ABSTRACT  
 
Immunotherapy targeting of amyloid beta (Abeta) peptide in transgenic mouse models of Alzheimer disease (AD) has been widely demonstrated to resolve amyloid deposition as well as associated neuronal, glial, and inflammatory pathologies. These successes have provided the basis for ongoing clinical trials of immunotherapy for treatment of AD in humans. Acute as well as chronic Abeta-targeted immunotherapy has also been demonstrated to reverse Abeta-related behavioral deficits assessing memory in AD transgenic mouse models. We observe that three antibodies targeting the same linear epitope of Abeta, Abeta(3-7), differ in their ability to reverse contextual fear deficits in Tg2576 mice in an acute testing paradigm. Reversal of contextual fear deficit by the antibodies does not correlate with in vitro recognition of Abeta in a consistent or correlative manner. To better define differences in antigen recognition at the atomic level, we determined crystal structures of Fab fragments in complex with Abeta. The conformation of the Abeta peptide recognized by all three antibodies was highly related and is also remarkably similar to that observed in independently reported Abeta:antibody crystal structures. Sequence and structural differences between the antibodies, particularly in CDR3 of the heavy chain variable region, are proposed to account for differing in vivo properties of the antibodies under study. These findings provide a structural basis for immunotherapeutic strategies targeting Abeta species postulated to underlie cognitive deficits in AD.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20970857 R.Robert, M.P.Lefranc, A.Ghochikyan, M.G.Agadjanyan, D.H.Cribbs, W.E.Van Nostrand, K.L.Wark, and O.Dolezal (2010).
Restricted V gene usage and VH/VL pairing of mouse humoral response against the N-terminal immunodominant epitope of the amyloid β peptide.
  Mol Immunol, 48, 59-72.  
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.