2iep

From Proteopedia

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 with SO4 as ligand. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 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

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