4MY2

Crystal Structure of Norrin in fusion with Maltose Binding Protein

4MY2 の概要

• エントリーDOI: 10.2210/pdb4my2/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Maltose-binding periplasmic protein, Norrin fusion protein, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose (3 entities in total)
• 機能のキーワード: cystine-knot growth factor, wnt signaling, cysteine-rich protein, angiogenesis, eye development, wnt/beta-catenin signaling, frizzled 4 receptor, lrp5/6, extracellular, fusion protein, signaling protein
• 由来する生物種: Escherichia coli O157:H7; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53177.46

構造登録者

Ke, J.,Jurecky, C.,Chen, C.,Gu, X.,Parker, N.,Williams, B.O.,Melcher, K.,Xu, H.E. (登録日: 2013-09-27, 公開日: 2013-11-13, 最終更新日: 2024-10-30)

主引用文献

Ke, J.,Harikumar, K.G.,Erice, C.,Chen, C.,Gu, X.,Wang, L.,Parker, N.,Cheng, Z.,Xu, W.,Williams, B.O.,Melcher, K.,Miller, L.J.,Xu, H.E.
Structure and function of Norrin in assembly and activation of a Frizzled 4-Lrp5/6 complex.
Genes Dev., 27:2305-2319, 2013

PubMed Abstract: Norrin is a cysteine-rich growth factor that is required for angiogenesis in the eye, ear, brain, and female reproductive organs. It functions as an atypical Wnt ligand by specifically binding to the Frizzled 4 (Fz4) receptor. Here we report the crystal structure of Norrin, which reveals a unique dimeric structure with each monomer adopting a conserved cystine knot fold. Functional studies demonstrate that the novel Norrin dimer interface is required for Fz4 activation. Furthermore, we demonstrate that Norrin contains separate binding sites for Fz4 and for the Wnt ligand coreceptor Lrp5 (low-density lipoprotein-related protein 5) or Lrp6. Instead of inducing Fz4 dimerization, Norrin induces the formation of a ternary complex with Fz4 and Lrp5/6 by binding to their respective extracellular domains. These results provide crucial insights into the assembly and activation of the Norrin-Fz4-Lrp5/6 signaling complex.

PubMed: 24186977
DOI: 10.1101/gad.228544.113

実験手法

X-RAY DIFFRACTION (2.4 Å)