3HKL

Crystal Structure of the Frizzled-like Cysteine-rich Domain of MuSK

Summary for 3HKL

• Entry DOI: 10.2210/pdb3hkl/pdb
• Descriptor: Muscle, skeletal receptor tyrosine protein kinase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: musk, receptor tyrosine kinase, frizzled crd, atp-binding, disulfide bond, glycoprotein, immunoglobulin domain, kinase, membrane, nucleotide-binding, phosphoprotein, receptor, transmembrane, tyrosine-protein kinase, transferase, signaling protein
• Biological source: Rattus norvegicus (rat)
• Total number of polymer chains: 2
• Total formula weight: 44624.93

Authors

Stiegler, A.L.,Hubbard, S.R. (deposition date: 2009-05-24, release date: 2009-08-25, Last modification date: 2024-10-30)

Primary citation

Stiegler, A.L.,Burden, S.J.,Hubbard, S.R.
Crystal structure of the frizzled-like cysteine-rich domain of the receptor tyrosine kinase MuSK.
J.Mol.Biol., 393:1-9, 2009

PubMed 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.

PubMed: 19664639
DOI: 10.1016/j.jmb.2009.07.091

Experimental method

X-RAY DIFFRACTION (2.1 Å)