6POL

Crystal structure of the human NELL1 EGF1-3-Robo3 FN1 complex

6POL の概要

• エントリーDOI: 10.2210/pdb6pol/pdb
• 関連するPDBエントリー: 6POG 6POK
• 分子名称: Roundabout homolog 3, Protein kinase C-binding protein NELL1, NITRATE ION, ... (7 entities in total)
• 機能のキーワード: axon guidance, nervous system, heterodimeric complex, glycoprotein, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 84493.05

構造登録者

Wang, J.,Pak, J.S.,Ozkan, E. (登録日: 2019-07-04, 公開日: 2020-05-06, 最終更新日: 2024-10-23)

主引用文献

Pak, J.S.,DeLoughery, Z.J.,Wang, J.,Acharya, N.,Park, Y.,Jaworski, A.,Ozkan, E.
NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance.
Nat Commun, 11:1489-1489, 2020

PubMed Abstract: Axon pathfinding is critical for nervous system development, and it is orchestrated by molecular cues that activate receptors on the axonal growth cone. Robo family receptors bind Slit guidance cues to mediate axon repulsion. In mammals, the divergent family member Robo3 does not bind Slits, but instead signals axon repulsion from its own ligand, NELL2. Conversely, canonical Robos do not mediate NELL2 signaling. Here, we present the structures of NELL-Robo3 complexes, identifying a mode of ligand engagement for Robos that is orthogonal to Slit binding. We elucidate the structural basis for differential binding between NELL and Robo family members and show that NELL2 repulsive activity is a function of its Robo3 affinity and is enhanced by ligand trimerization. Our results reveal a mechanism of oligomerization-induced Robo activation for axon guidance and shed light on Robo family member ligand binding specificity, conformational variability, divergent modes of signaling, and evolution.

PubMed: 32198364
DOI: 10.1038/s41467-020-15211-1

実験手法

X-RAY DIFFRACTION (1.8 Å)