3BKJ
Crystal structure of Fab wo2 bound to the n terminal domain of amyloid beta peptide (1-16)
Summary for 3BKJ
| Entry DOI | 10.2210/pdb3bkj/pdb |
| Related | 3BAE 3BKC 3BKM |
| Descriptor | WO2 IgG2a Fab fragment Light Chain Kappa, WO2 IgG2a Fab fragment Heavy Chain, Amyloid Beta Peptide, ... (4 entities in total) |
| Functional Keywords | abeta, amyloid beta peptide, fab, wo2, alzheimer's disease, immunotherapies, app, immune system |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 3 |
| Total formula weight | 54210.81 |
| Authors | Miles, L.A.,Wun, K.S.,Crespi, G.A.,Fodero-Tavoletti, M.,Galatis, D.,Bageley, C.J.,Beyreuther, K.,Masters, C.L.,Cappai, R.,McKinstry, W.J.,Barnham, K.J.,Parker, M.W. (deposition date: 2007-12-06, release date: 2008-04-15, Last modification date: 2024-10-16) |
| Primary citation | Miles, L.A.,Wun, K.S.,Crespi, G.A.,Fodero-Tavoletti, M.T.,Galatis, D.,Bagley, C.J.,Beyreuther, K.,Masters, C.L.,Cappai, R.,McKinstry, W.J.,Barnham, K.J.,Parker, M.W. Amyloid-beta-anti-amyloid-beta complex structure reveals an extended conformation in the immunodominant B-cell epitope. J.Mol.Biol., 377:181-192, 2008 Cited by PubMed Abstract: Alzheimer's disease (AD) is the most common form of dementia. Amyloid-beta (A beta) peptide, generated by proteolytic cleavage of the amyloid precursor protein, is central to AD pathogenesis. Most pharmaceutical activity in AD research has focused on A beta, its generation and clearance from the brain. In particular, there is much interest in immunotherapy approaches with a number of anti-A beta antibodies in clinical trials. We have developed a monoclonal antibody, called WO2, which recognises the A beta peptide. To this end, we have determined the three-dimensional structure, to near atomic resolution, of both the antibody and the complex with its antigen, the A beta peptide. The structures reveal the molecular basis for WO2 recognition and binding of A beta. The A beta peptide adopts an extended, coil-like conformation across its major immunodominant B-cell epitope between residues 2 and 8. We have also studied the antibody-bound A beta peptide in the presence of metals known to affect its aggregation state and show that WO2 inhibits these interactions. Thus, antibodies that target the N-terminal region of A beta, such as WO2, hold promise for therapeutic development. PubMed: 18237744DOI: 10.1016/j.jmb.2007.12.036 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.59 Å) |
Structure validation
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