8S9P

1:1:1 agrin/LRP4/MuSK complex

Summary for 8S9P

• Entry DOI: 10.2210/pdb8s9p/pdb
• EMDB information: 40241
• Descriptor: Agrin, Low-density lipoprotein receptor-related protein 4, Muscle, skeletal receptor tyrosine-protein kinase (3 entities in total)
• Functional Keywords: agrin, lrp4, musk, nmj, rtk, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 527004.18

Authors

Xie, T.,Xu, G.J.,Liu, Y.,Quade, B.,Lin, W.C.,Bai, X.C. (deposition date: 2023-03-29, release date: 2023-05-17, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.8 Å)