1luf
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='1luf' size='340' side='right'caption='[[1luf]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='1luf' size='340' side='right'caption='[[1luf]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1luf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <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> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
<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> | <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> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [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> | |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 19: | Line 19: | ||
</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]. | </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]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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. | ||
| - | |||
| - | 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<ref>PMID:12220490</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1luf" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]] | + | *[[Tyrosine kinase receptor 3D structures|Tyrosine kinase receptor 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Buffalo rat]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Becerra | + | [[Category: Becerra M]] |
| - | [[Category: Burden | + | [[Category: Burden SJ]] |
| - | [[Category: Hubbard | + | [[Category: Hubbard SR]] |
| - | [[Category: Lu | + | [[Category: Lu Y]] |
| - | [[Category: Ma | + | [[Category: Ma Y]] |
| - | [[Category: Neubert | + | [[Category: Neubert TA]] |
| - | [[Category: Till | + | [[Category: Till JH]] |
| - | [[Category: Watty | + | [[Category: Watty A]] |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation
| |||||||||||
Categories: Large Structures | Rattus norvegicus | Becerra M | Burden SJ | Hubbard SR | Lu Y | Ma Y | Neubert TA | Till JH | Watty A
