8S9P

1:1:1 agrin/LRP4/MuSK complex

8S9P の概要

• エントリーDOI: 10.2210/pdb8s9p/pdb
• EMDBエントリー: 40241
• 分子名称: Agrin, Low-density lipoprotein receptor-related protein 4, Muscle, skeletal receptor tyrosine-protein kinase (3 entities in total)
• 機能のキーワード: agrin, lrp4, musk, nmj, rtk, 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: 527004.18

構造登録者

Xie, T.,Xu, G.J.,Liu, Y.,Quade, B.,Lin, W.C.,Bai, X.C. (登録日: 2023-03-29, 公開日: 2023-05-17, 最終更新日: 2024-11-13)

主引用文献

Xie, T.,Xu, G.,Liu, Y.,Quade, B.,Lin, W.,Bai, X.C.
Structural insights into the assembly of the agrin/LRP4/MuSK signaling complex.
Proc.Natl.Acad.Sci.USA, 120:e2300453120-e2300453120, 2023

PubMed Abstract: MuSK is a receptor tyrosine kinase (RTK) that plays essential roles in the formation and maintenance of the neuromuscular junction. Distinct from most members of RTK family, MuSK activation requires not only its cognate ligand agrin but also its coreceptors LRP4. However, how agrin and LRP4 coactivate MuSK remains unclear. Here, we report the cryo-EM structure of the extracellular ternary complex of agrin/LRP4/MuSK in a stoichiometry of 1:1:1. This structure reveals that arc-shaped LRP4 simultaneously recruits both agrin and MuSK to its central cavity, thereby promoting a direct interaction between agrin and MuSK. Our cryo-EM analyses therefore uncover the assembly mechanism of agrin/LRP4/MuSK signaling complex and reveal how MuSK receptor is activated by concurrent binding of agrin and LRP4.

PubMed: 37252960
DOI: 10.1073/pnas.2300453120

実験手法

ELECTRON MICROSCOPY (3.8 Å)