3o11

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

spinqualitylabelsall models 3o11, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3o11 is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: PCA Related: 3mcl Gene: IGKC (LK3 transgenic mice), IGHG1 (LK3 transgenic mice) Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Alzheimer's disease is a progressive neurodegenerative disease characterized by extracellular deposits of beta-amyloid (Abeta) plaques. Aggregation of the Abeta(42) peptide leading to plaque formation is believed to play a central role in Alzheimer's disease pathogenesis. Anti-Abeta monoclonal antibodies can reduce amyloid plaques and could possibly be used for immunotherapy. We have developed a monoclonal antibody C706, which recognizes the human Abeta peptide. Here we report the crystal structure of the antibody Fab fragment at 1.7 A resolution. The structure was determined in two crystal forms, P2(1) and C2. Although the Fab was crystallized in the presence of Abeta(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 Abeta recognition by antibodies PFA1 and WO2. All three antibodies recognize the same immunodominant B-cell epitope of Abeta. By similarity, residues Phe-Arg-His of Abeta would be a major portion of the C706 epitope. Copyright (c) 2010 John Wiley & Sons, Ltd. His-tag binding by antibody C706 mimics beta-amyloid recognition.,Teplyakov A, Obmolova G, Canziani G, Zhao Y, Gutshall L, Jung SS, Gilliland GL J Mol Recognit. 2010 Sep 14. PMID:20842634 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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