Title : Crystal structure of the frizzled-like
cysteine-rich
domain of the receptor
tyrosine kinase
MuSK
Abstract :
- Muscle-specific kinase ( MuSK ) is an essential receptor tyrosine kinase for the establishment and maintenance of the neuromuscular junction (NMJ)
- Activation of MuSK by agrin , a neuronally derived heparan-sulfate proteoglycan , and LRP4 ( low-density lipoprotein receptor-related protein-4 ), the agrin receptor , leads to clustering of acetylcholine receptors on the postsynaptic side of the NMJ
- The ectodomain of MuSK comprises three immunoglobulin-like domains and a cysteine-rich domain (Fz-CRD) related to those in Frizzled proteins , the receptors for Wnts
- Here, we report the crystal structure of the MuSK Fz-CRD at 2.1 A resolution
- The structure reveals a five-disulfide-bridged domain similar to CRDs of Frizzled proteins but with a divergent C-terminal region
- An asymmetric dimer present in the crystal structure implicates surface hydrophobic residues that may function in homotypic or heterotypic interactions to mediate co-clustering of MuSK , rapsyn , and acetylcholine receptors at the NMJ