4hbc

Crystal structure of a conformation-dependent rabbit IgG Fab specific for amyloid prefibrillar oligomers

spinqualitylabelsall models 4hbc, resolution 1.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hbc is a 2 chain structure with sequence from European rabbit. This structure supersedes the now removed PDB entry 3nl4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed BACKGROUND: Although rabbit antibodies are widely used in research, no structures of rabbit antigen-binding fragments (Fab) have been reported. M204 is a rabbit monoclonal antibody that recognizes a generic epitope that is common to prefibrillar amyloid oligomers formed from many different amyloidogenic sequences. Amyloid oligomers are widely suspected to be a primary causative agent of pathogenesis in several age-related neurodegenerative diseases, such as Alzheimer's disease. The detailed structure of these amyloid oligomers is not known nor is the mechanism for the recognition of the generic epitope by conformation-dependent monoclonal antibodies. METHOD: As a first approach to understanding the mechanism of conformation-dependent antibody recognition, we have crystallized the Fab of M204. RESULTS: We have determined the structure of the Fab of M204 at 1.54A resolution. The crystal structure reveals details of the M204 antigen combining site and features unique to rabbit Fabs such as an interdomain disulfide bond on its light chain. GENERAL SIGNIFICANCE: Based on the structural features of the antigen-combining site of the M204, we rule out a "steric zipper" formation, as found in numerous amyloid fibril structures, as a mechanism of antibody-antigen recognition. The details of the first rabbit immunoglobulin Fab structure might also be useful for exploiting the potential of rabbit monoclonal antibodies for the development of humanized rabbit antibodies as therapeutic agents. Crystal structure of a conformation-dependent rabbit IgG Fab specific for amyloid prefibrillar oligomers.,Arai H, Glabe C, Luecke H Biochim Biophys Acta. 2012 Dec;1820(12):1908-14. doi:, 10.1016/j.bbagen.2012.08.016. Epub 2012 Aug 24. PMID:22940003 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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