The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody |
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Authors: | Chavali Gayatri B Papageorgiou Anastassios C Olson Karen A Fett James W Hu Guo fu Shapiro Robert Acharya K Ravi |
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Institution: | Department of Biology and Biochemistry, University of Bath, Claverton Down, BA2 7AY, Bath, United Kingdom. |
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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. |
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