1luf

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(New page: 200px<br /><applet load="1luf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1luf, resolution 2.05&Aring;" /> '''Crystal Structure of...)
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[[Image:1luf.gif|left|200px]]<br /><applet load="1luf" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1luf, resolution 2.05&Aring;" />
 
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'''Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation'''<br />
 
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==Overview==
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==Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation==
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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.
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<StructureSection load='1luf' size='340' side='right'caption='[[1luf]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1luf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LUF FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1luf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1luf OCA], [https://pdbe.org/1luf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1luf RCSB], [https://www.ebi.ac.uk/pdbsum/1luf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1luf ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MUSK_RAT MUSK_RAT] Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle. Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation.<ref>PMID:16870737</ref> <ref>PMID:17011580</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lu/1luf_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1luf ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LUF OCA].
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*[[Tyrosine kinase receptor 3D structures|Tyrosine kinase receptor 3D structures]]
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== References ==
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==Reference==
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<references/>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12220490 12220490]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Becerra M]]
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[[Category: Transferase]]
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[[Category: Burden SJ]]
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[[Category: Becerra, M.]]
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[[Category: Hubbard SR]]
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[[Category: Burden, S.J.]]
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[[Category: Lu Y]]
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[[Category: Hubbard, S.R.]]
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[[Category: Ma Y]]
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[[Category: Lu, Y.]]
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[[Category: Neubert TA]]
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[[Category: Ma, Y.]]
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[[Category: Till JH]]
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[[Category: Neubert, T.A.]]
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[[Category: Watty A]]
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[[Category: Till, J.H.]]
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[[Category: Watty, A.]]
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[[Category: mass spectrometry]]
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[[Category: phosphorylation]]
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[[Category: signal transduction]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:53:51 2007''
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Current revision

Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation

PDB ID 1luf

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