Journal
STRUCTURE
Volume 19, Issue 8, Pages 1097-1107Publisher
CELL PRESS
DOI: 10.1016/j.str.2011.01.019
Keywords
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Funding
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-98CH10886, DE-AC02-06CH11357]
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The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonover-lapping among the three contact patches.
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