3O11

Anti-beta-amyloid antibody c706 fab in space group c2

Summary for 3O11

• Entry DOI: 10.2210/pdb3o11/pdb
• Related: 3MCL
• Descriptor: C706 LIGHT CHAIN variable region, Ig kappa chain C region chimera, C706 HEAVY CHAIN variable region, Ig gamma-1 chain C region chimera (3 entities in total)
• Functional Keywords: immunoglobulin fold, immune system
• Biological source: Mus musculus (mouse, human); More
• Total number of polymer chains: 4
• Total formula weight: 94517.06

Authors

Teplyakov, A.,Obmolova, G.,Malia, T.,Gilliland, G.L. (deposition date: 2010-07-20, release date: 2010-09-08, Last modification date: 2024-10-16)

Primary citation

Teplyakov, A.,Obmolova, G.,Canziani, G.,Zhao, Y.,Gutshall, L.,Jung, S.S.,Gilliland, G.L.
His-tag binding by antibody C706 mimics beta-amyloid recognition.
J.Mol.Recognit., 24:570-575, 2011

PubMed Abstract: Alzheimer's disease is a progressive neurodegenerative disease characterized by extracellular deposits of β-amyloid (Aβ) plaques. Aggregation of the Aβ(42) peptide leading to plaque formation is believed to play a central role in Alzheimer's disease pathogenesis. Anti-Aβ monoclonal antibodies can reduce amyloid plaques and could possibly be used for immunotherapy. We have developed a monoclonal antibody C706, which recognizes the human Aβ peptide. Here we report the crystal structure of the antibody Fab fragment at 1.7 Å resolution. The structure was determined in two crystal forms, P2(1) and C2. Although the Fab was crystallized in the presence of Aβ(16), no peptide was observed in the crystals. The antigen-binding site is blocked by the hexahistidine tag of another Fab molecule in both crystal forms. The poly-His peptide in an extended conformation occupies a crevice between the light and heavy chains of the variable domain. Two consecutive histidines (His4-His5) stack against tryptophan residues in the central pocket of the antigen-binding surface. In addition, they form hydrogen bonds to the acidic residues at the bottom of the pocket. The mode of his-tag binding by C706 resembles the Aβ recognition by antibodies PFA1 and WO2. All three antibodies recognize the same immunodominant B-cell epitope of Aβ. By similarity, residues Phe-Arg-His of Aβ would be a major portion of the C706 epitope.

PubMed: 20842634
DOI: 10.1002/jmr.1069

Experimental method

X-RAY DIFFRACTION (2.8 Å)