1luf
From Proteopedia
(New page: 200px<br /><applet load="1luf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1luf, resolution 2.05Å" /> '''Crystal Structure of...) |
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| - | [[Image:1luf.gif|left|200px]]<br /><applet load="1luf" size=" | + | [[Image:1luf.gif|left|200px]]<br /><applet load="1luf" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1luf, resolution 2.05Å" /> | caption="1luf, resolution 2.05Å" /> | ||
'''Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation'''<br /> | '''Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed | + | Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed selectively in skeletal muscle. During neuromuscular synapse formation, agrin released from motor neurons stimulates MuSK autophosphorylation in the kinase activation loop and in the juxtamembrane region, leading to clustering of acetylcholine receptors. We have determined the crystal structure of the cytoplasmic domain of unphosphorylated MuSK at 2.05 A resolution. The structure reveals an autoinhibited kinase domain in which the activation loop obstructs ATP and substrate binding. Steady-state kinetic analysis demonstrates that autophosphorylation results in a 200-fold increase in k(cat) and a 10-fold decrease in the K(m) for ATP. These studies provide a molecular basis for understanding the regulation of MuSK catalytic activity and suggest that an additional in vivo component may contribute to regulation via the juxtamembrane region. |
==About this Structure== | ==About this Structure== | ||
| - | 1LUF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http:// | + | 1LUF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LUF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Becerra, M.]] | [[Category: Becerra, M.]] | ||
| - | [[Category: Burden, S | + | [[Category: Burden, S J.]] |
| - | [[Category: Hubbard, S | + | [[Category: Hubbard, S R.]] |
[[Category: Lu, Y.]] | [[Category: Lu, Y.]] | ||
[[Category: Ma, Y.]] | [[Category: Ma, Y.]] | ||
| - | [[Category: Neubert, T | + | [[Category: Neubert, T A.]] |
| - | [[Category: Till, J | + | [[Category: Till, J H.]] |
[[Category: Watty, A.]] | [[Category: Watty, A.]] | ||
[[Category: mass spectrometry]] | [[Category: mass spectrometry]] | ||
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[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:48:36 2008'' |
Revision as of 11:48, 21 February 2008
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Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation
Overview
Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed selectively in skeletal muscle. During neuromuscular synapse formation, agrin released from motor neurons stimulates MuSK autophosphorylation in the kinase activation loop and in the juxtamembrane region, leading to clustering of acetylcholine receptors. We have determined the crystal structure of the cytoplasmic domain of unphosphorylated MuSK at 2.05 A resolution. The structure reveals an autoinhibited kinase domain in which the activation loop obstructs ATP and substrate binding. Steady-state kinetic analysis demonstrates that autophosphorylation results in a 200-fold increase in k(cat) and a 10-fold decrease in the K(m) for ATP. These studies provide a molecular basis for understanding the regulation of MuSK catalytic activity and suggest that an additional in vivo component may contribute to regulation via the juxtamembrane region.
About this Structure
1LUF is a Single protein structure of sequence from Rattus norvegicus. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation., Till JH, Becerra M, Watty A, Lu Y, Ma Y, Neubert TA, Burden SJ, Hubbard SR, Structure. 2002 Sep;10(9):1187-96. PMID:12220490
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