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'''Crystal structure of immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK''' | '''Crystal structure of immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK''' | ||
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[[Category: Hubbard, S R.]] | [[Category: Hubbard, S R.]] | ||
[[Category: Stiegler, A L.]] | [[Category: Stiegler, A L.]] | ||
[[Category: | [[Category: Beta-sandwich]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:25:13 2008'' | |||
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Revision as of 04:25, 4 May 2008
Crystal structure of immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK
Overview
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.
About this Structure
2IEP is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK., Stiegler AL, Burden SJ, Hubbard SR, J Mol Biol. 2006 Dec 1;364(3):424-33. Epub 2006 Sep 12. PMID:17011580 Page seeded by OCA on Sun May 4 07:25:13 2008