4o27: Difference between revisions
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''' | ==Crystal structure of MST3-MO25 complex with WIF motif== | ||
<StructureSection load='4o27' size='340' side='right' caption='[[4o27]], [[Resolution|resolution]] 3.19Å' scene=''> | |||
== 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> | |||
</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> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nzw|4nzw]]</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'>[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://www.rcsb.org/pdb/explore.do?structureId=4o27 RCSB], [http://www.ebi.ac.uk/pdbsum/4o27 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:24746913</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Non-specific serine/threonine protein kinase]] | |||
[[Category: Feng, M]] | |||
[[Category: Hao, Q]] | |||
[[Category: Zhou, Z C]] | |||
[[Category: Protein ser/thr kinase]] | |||
[[Category: Scaffold protein]] | |||
[[Category: Signaling protein]] | |||
[[Category: Transferase activator-transferase complex]] | |||
Revision as of 12:24, 3 December 2014
Crystal structure of MST3-MO25 complex with WIF motifCrystal structure of MST3-MO25 complex with WIF motif
Structural highlights
Publication Abstract from PubMedThe 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. References
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