2QQK

Neuropilin-2 a1a2b1b2 Domains in Complex with a Semaphorin-Blocking Fab

2QQK の概要

• エントリーDOI: 10.2210/pdb2qqk/pdb
• 関連するPDBエントリー: 2QQI 2QQJ 2QQL 2QQM 2QQN 2QQO
• 分子名称: Neuropilin-2, Antibody Heavy Chain, Antibody Light Chain, ... (4 entities in total)
• 機能のキーワード: vegf receptor, semaphorin receptor, phage-derived antibody, developmental protein, differentiation, glycoprotein, membrane, neurogenesis, transmembrane, hormone, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 114018.45

構造登録者

Appleton, B.A.,Wiesmann, C. (登録日: 2007-07-26, 公開日: 2007-11-20, 最終更新日: 2024-11-06)

主引用文献

Appleton, B.A.,Wu, P.,Maloney, J.,Yin, J.,Liang, W.C.,Stawicki, S.,Mortara, K.,Bowman, K.K.,Elliott, J.M.,Desmarais, W.,Bazan, J.F.,Bagri, A.,Tessier-Lavigne, M.,Koch, A.W.,Wu, Y.,Watts, R.J.,Wiesmann, C.
Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding
Embo J., 26:4902-4912, 2007

PubMed Abstract: Neuropilins (Nrps) are co-receptors for class 3 semaphorins and vascular endothelial growth factors and important for the development of the nervous system and the vasculature. The extracellular portion of Nrp is composed of two domains that are essential for semaphorin binding (a1a2), two domains necessary for VEGF binding (b1b2), and one domain critical for receptor dimerization (c). We report several crystal structures of Nrp1 and Nrp2 fragments alone and in complex with antibodies that selectively block either semaphorin or vascular endothelial growth factor (VEGF) binding. In these structures, Nrps adopt an unexpected domain arrangement in which the a2, b1, and b2 domains form a tightly packed core that is only loosely connected to the a1 domain. The locations of the antibody epitopes together with in vitro experiments indicate that VEGF and semaphorin do not directly compete for Nrp binding. Based upon our structural and functional data, we propose possible models for ligand binding to neuropilins.

PubMed: 17989695
DOI: 10.1038/sj.emboj.7601906

実験手法

X-RAY DIFFRACTION (2.75 Å)