title: Crystal structure of a conformation-dependent rabbit IgG Fab specific for amyloid prefibrillar oligomers.
abstract: 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.
  
  
  METHODS
  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 1.54Å 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Arai
authors.forename: Charles
authors.initials: C
authors.lastname: Glabe
authors.forename: Hartmut
authors.initials: H
authors.lastname: Luecke
mesh_terms: D000682:Amyloid / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001666:Binding Sites, Antibody; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011817:Rabbits
chemical_list: D000682:Amyloid; D000911:Antibodies, Monoclonal; D004220:Disulfides; D007140:Immunoglobulin Fab Fragments