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Crystal Structure of Vascular Endothelial Growth Factor-B in Complex with a Neutralising Antibody Fab Fragment


Reference:

Leonard, P., Scotney, P. D., Jabeen, T., Iyer, S., Fabri, L. J., Nash, A. D. and Acharya, K. R., 2008. Crystal Structure of Vascular Endothelial Growth Factor-B in Complex with a Neutralising Antibody Fab Fragment. Journal of Molecular Biology, 384 (5), pp. 1203-1217.

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http://dx.doi.org/10.1016/j.jmb.2008.09.076

Abstract

Vascular endothelial growth factor (VEGF) B effects blood vessel formation by binding to VEGF receptor 1. To study the specifics of the biological profile of VEGF-B in both physiological and pathological angiogenesis, a neutralising anti-VEGF-B antibody (2H10) that functions by inhibiting the balding of VEGF-B to VEGF receptor 1. was developed. Here, we present the structural features of the 'highly ordered' interaction of the Fab fragment of this antibody (Fab-2H10) with VEGF-B. Two molecules of Fab-2H10 bind to symmetrical binding sites located at each pole of the VEGF-B homodimer, giving a unique U-shaped topology to the complex that has not been previously observed in the VEGF family. VEGF-B residues essential for binding to the antibody are contributed by both monomers of the cytokine. Our detailed analysis reveals that the neutralising effect of the antibody occurs by virtue of the steric hindrance of the receptor-binding interface. These findings suggest that functional complementarity between VEGF-B and 2H10 can be harnessed both in analysing the therapeutic potential of VEGF-B and as an antagonist of receptor activation. (C) 2008 Elsevier Ltd. All rights reserved.

Details

Item Type Articles
CreatorsLeonard, P., Scotney, P. D., Jabeen, T., Iyer, S., Fabri, L. J., Nash, A. D. and Acharya, K. R.
DOI10.1016/j.jmb.2008.09.076
Uncontrolled Keywordsx-ray crystallography, neutralising antibody, angiogenesis, vegf-b center dot fab complex, vegf-b
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code12416

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