title: The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody.
abstract: The murine monoclonal antibody 26-2F neutralizes the angiogenic and ribonucleolytic activities of human angiogenin (ANG) and is highly effective in preventing the establishment and metastatic dissemination of human tumors in athymic mice. Here we report a 2.0 A resolution crystal structure for the complex of ANG with the Fab fragment of 26-2F that reveals the detailed interactions between ANG and the complementarity-determining regions (CDRs) of the antibody. Surprisingly, Fab binding induces a dramatic conformational change in the cell binding region of ANG at the opposite end of the molecule from the combining site; crosslinking experiments indicate that this rearrangement also occurs in solution. The ANG-Fab complex structure should be invaluable for designing maximally humanized versions of 26-2F for potential clinical use.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, BA2 7AY, Bath, United Kingdom.
authors.forename: Gayatri B
authors.initials: GB
authors.lastname: Chavali
authors.forename: Anastassios C
authors.initials: AC
authors.lastname: Papageorgiou
authors.forename: Karen A
authors.initials: KA
authors.lastname: Olson
authors.forename: James W
authors.initials: JW
authors.lastname: Fett
authors.forename: Guo fu
authors.initials: Gf
authors.lastname: Hu
authors.forename: Robert
authors.initials: R
authors.lastname: Shapiro
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
mesh_terms: D000595:Amino Acid Sequence; D022801:Complementarity Determining Regions; D018604:Epitope Mapping; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology*; D009500:Neutralization Tests; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000276:immunology
chemical_list: D022801:Complementarity Determining Regions; D007140:Immunoglobulin Fab Fragments; C046366:angiogenin; D012259:Ribonuclease, Pancreatic