2VWE

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

2VWE の概要

• エントリーDOI: 10.2210/pdb2vwe/pdb
• 関連するPDBエントリー: 2C7W
• 分子名称: VASCULAR ENDOTHELIAL GROWTH FACTOR B, ANTI-VEGF-B MONOCLONAL ANTIBODY (3 entities in total)
• 機能のキーワード: immune system, glycoprotein, cysteine-knot, growth factor, vegf-b, mitogen, secreted, angiogenesis, neutralizing antibody, heparin-binding
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Secreted: P49765
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 132355.25

構造登録者

Leonard, P.,Scotney, P.D.,Jabeen, T.,Iyer, S.,Fabri, L.J.,Nash, A.D.,Acharya, K.R. (登録日: 2008-06-23, 公開日: 2008-11-04, 最終更新日: 2024-11-20)

主引用文献

Leonard, P.,Scotney, P.D.,Jabeen, T.,Iyer, S.,Fabri, L.J.,Nash, A.D.,Acharya, K.R.
Crystal Structure of Vascular Endothelial Growth Factor-B in Complex with a Neutralising Antibody Fab Fragment.
J.Mol.Biol., 384:1203-, 2008

PubMed 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 binding 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.

PubMed: 18930733
DOI: 10.1016/J.JMB.2008.09.076

実験手法

X-RAY DIFFRACTION (3.4 Å)