Crystal Structure of the Frizzled-Like Cysteine-Rich Domain of the Receptor Tyrosine Kinase MuSK
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 {angstrom} 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.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 980108
- Report Number(s):
- BNL--93026-2010-JA
- Journal Information:
- Journal of Molecular Biology, Journal Name: Journal of Molecular Biology Journal Issue: 1 Vol. 393; ISSN JMOBAK; ISSN 0022-2836
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ACETYLCHOLINE
CRYSTAL STRUCTURE
DIMERS
FUNCTIONS
INTERACTIONS
LIPOPROTEINS
MAINTENANCE
PHOSPHOTRANSFERASES
PROTEINS
RECEPTORS
RESIDUES
RESOLUTION
SURFACES
TYROSINE
national synchrotron light source