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2iep
From Proteopedia
(New page: 200px<br /><applet load="2iep" size="450" color="white" frame="true" align="right" spinBox="true" caption="2iep, resolution 2.205Å" /> '''Crystal structure o...) |
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| - | [[Image:2iep.gif|left|200px]]<br /><applet load="2iep" size=" | + | [[Image:2iep.gif|left|200px]]<br /><applet load="2iep" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2iep, resolution 2.205Å" /> | caption="2iep, resolution 2.205Å" /> | ||
'''Crystal structure of immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK'''<br /> | '''Crystal structure of immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed | + | 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== | ==About this Structure== | ||
| - | 2IEP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http:// | + | 2IEP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IEP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Burden, S | + | [[Category: Burden, S J.]] |
| - | [[Category: Hubbard, S | + | [[Category: Hubbard, S R.]] |
| - | [[Category: Stiegler, A | + | [[Category: Stiegler, A L.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: beta-sandwich]] | [[Category: beta-sandwich]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:51:54 2008'' |
Revision as of 15:51, 21 February 2008
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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 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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