2IEP: Crystal Structure Of Immunoglobulin-like Domains 1 And 2 Of The Receptor Tyrosine Kinase Musk

Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively in skeletal muscle, where it is required for formation of the neuromuscular junction. MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. Here, we report the crystal structure of the agrin-responsive first and second immunoglobulin-like domains (Ig1 and Ig2) of the MuSK ectodomain at 2.2 A resolution. The structure reveals that MuSK Ig1 and Ig2 are Ig-like domains of the I-set subfamily, which are configured in a linear, semi-rigid arrangement. In addition to the canonical internal disulfide bridge, Ig1 contains a second, solvent-exposed disulfide bridge, which our biochemical data indicate is critical for proper folding of Ig1 and processing of MuSK. Two Ig1-2 molecules form a non-crystallographic dimer that is mediated by a unique hydrophobic patch on the surface of Ig1. Biochemical analyses of MuSK mutants introduced into MuSK(-/-) myotubes demonstrate that residues in this hydrophobic patch are critical for agrin-induced MuSK activation.
PDB ID: 2IEPDownload
MMDB ID: 42940
PDB Deposition Date: 2006/9/19
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2.21  Å
Source Organism:
Similar Structures:
Biological Unit for 2IEP: dimeric; determined by author
Molecular Components in 2IEP
Label Count Molecule
Proteins (2 molecules)
Muscle-specific Kinase Receptor(Gene symbol: Musk)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB