2IEP
Crystal structure of immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK
Summary for 2IEP
| Entry DOI | 10.2210/pdb2iep/pdb |
| Descriptor | Muscle-specific kinase receptor, SULFATE ION (3 entities in total) |
| Functional Keywords | beta-sandwich, signaling protein, transferase |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cell junction, synapse, postsynaptic cell membrane ; Single-pass type I membrane protein : Q62838 |
| Total number of polymer chains | 2 |
| Total formula weight | 42182.61 |
| Authors | Stiegler, A.L.,Burden, S.J.,Hubbard, S.R. (deposition date: 2006-09-19, release date: 2006-11-28, Last modification date: 2024-11-13) |
| Primary citation | Stiegler, A.L.,Burden, S.J.,Hubbard, S.R. Crystal Structure of the Agrin-responsive Immunoglobulin-like Domains 1 and 2 of the Receptor Tyrosine Kinase MuSK J.Mol.Biol., 364:424-433, 2006 Cited by PubMed Abstract: 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. PubMed: 17011580DOI: 10.1016/j.jmb.2006.09.019 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.205 Å) |
Structure validation
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