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| | ==Crystal structure of MST3-MO25 complex with WIF motif== | | ==Crystal structure of MST3-MO25 complex with WIF motif== |
| - | <StructureSection load='4o27' size='340' side='right' caption='[[4o27]], [[Resolution|resolution]] 3.19Å' scene=''> | + | <StructureSection load='4o27' size='340' side='right'caption='[[4o27]], [[Resolution|resolution]] 3.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4o27]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O27 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4o27]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O27 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.185Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nzw|4nzw]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=4o27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o27 OCA], [https://pdbe.org/4o27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o27 RCSB], [https://www.ebi.ac.uk/pdbsum/4o27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o27 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o27 OCA], [http://pdbe.org/4o27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o27 RCSB], [http://www.ebi.ac.uk/pdbsum/4o27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o27 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CAB39_HUMAN CAB39_HUMAN]] Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1. [[http://www.uniprot.org/uniprot/STK24_HUMAN STK24_HUMAN]] Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. Regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.<ref>PMID:16314523</ref> <ref>PMID:17046825</ref> <ref>PMID:19604147</ref> <ref>PMID:19855390</ref> <ref>PMID:19782762</ref> | + | [https://www.uniprot.org/uniprot/CAB39_HUMAN CAB39_HUMAN] Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Feng, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Hao, Q]] | + | [[Category: Feng M]] |
| - | [[Category: Zhou, Z C]] | + | [[Category: Hao Q]] |
| - | [[Category: Protein ser/thr kinase]] | + | [[Category: Zhou ZC]] |
| - | [[Category: Scaffold protein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transferase activator-transferase complex]]
| + | |
| Structural highlights
Function
CAB39_HUMAN Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1.
Publication Abstract from PubMed
The tumor suppressor kinase LKB1 and germinal center kinases (GCKs) are key regulators of various cellular functions. The adaptor molecule MO25 not only recruits and activates LKB1 through the pseudokinase STRAD, but also may directly activate GCKs like MST3, MST4, STK25, OSR1 and SPAK. Targeting MO25 in a pathological setting has been recently studied in mouse. Yet the regulatory mechanism of MO25-mediated kinase activation is not fully understood. Here, our structural studies of MO25-related kinases reveal that MO25 binds to and activates GCK kinases or pseudokinase through a unified structural mechanism, featuring an active conformation of the alphaC helix and A-loop stabilized by MO25. Compared to GCKs that are directly activated by MO25-binding, activation of LKB1 has evolved additional layer of regulatory machinery, i.e., MO25 "activates" the pseudokinase STRAD, which in turn activates LKB1. Importantly, the structures of MO25alpha-STK25 and MO25alpha-MST3 determined in this work represent a transition/intermediate state and a fully activated state, respectively during the MO25-mediated kinase activating process.
Structural insights into regulatory mechanisms of MO25-mediated kinase activation.,Hao Q, Feng M, Shi Z, Li C, Chen M, Wang W, Zhang M, Jiao S, Zhou Z J Struct Biol. 2014 May;186(2):224-33. doi: 10.1016/j.jsb.2014.04.005. Epub 2014 , Apr 16. PMID:24746913[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hao Q, Feng M, Shi Z, Li C, Chen M, Wang W, Zhang M, Jiao S, Zhou Z. Structural insights into regulatory mechanisms of MO25-mediated kinase activation. J Struct Biol. 2014 May;186(2):224-33. doi: 10.1016/j.jsb.2014.04.005. Epub 2014 , Apr 16. PMID:24746913 doi:http://dx.doi.org/10.1016/j.jsb.2014.04.005
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