2a2a: Difference between revisions
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==High-resolution crystallographic analysis of the autoinhibited conformation of a human death-associated protein kinase== | |||
<StructureSection load='2a2a' size='340' side='right'caption='[[2a2a]], [[Resolution|resolution]] 1.47Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2a2a]] is a 4 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=2A2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A2A FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.47Å</td></tr> | |||
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=2a2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a2a OCA], [https://pdbe.org/2a2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a2a RCSB], [https://www.ebi.ac.uk/pdbsum/2a2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a2a ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DAPK2_HUMAN DAPK2_HUMAN] Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref> Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.<ref>PMID:10376525</ref> <ref>PMID:10629061</ref> <ref>PMID:21408167</ref> <ref>PMID:11230133</ref> <ref>PMID:11980920</ref> <ref>PMID:17347302</ref> <ref>PMID:18957423</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a2/2a2a_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2a2a ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The regulation of many protein kinases by binding to calcium/calmodulin connects two principal mechanisms in signaling processes: protein phosphorylation and responses to dose- and time-dependent calcium signals. We used the calcium/calmodulin-dependent members of the death-associated protein kinase (DAPK) family to investigate the role of a basic DAPK signature loop near the kinase active site. In DAPK2, this loop comprises a novel dimerization-regulated calcium/calmodulin-binding site, in addition to a well-established calcium/calmodulin site in the C-terminal autoregulatory domain. Unexpectedly, impairment of the basic loop interaction site completely abolishes calcium/calmodulin binding and DAPK2 activity is reduced to a residual level, indicative of coupled binding to the two sites. This contrasts with the generally accepted view that kinase calcium/calmodulin interactions are autonomous of the kinase catalytic domain. Our data establish an intricate model of multi-step kinase activation and expand our understanding of how calcium binding connects with other mechanisms involved in kinase activity regulation. | |||
Death-Associated Protein Kinase Activity Is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites.,Simon B, Huart AS, Temmerman K, Vahokoski J, Mertens HD, Komadina D, Hoffmann JE, Yumerefendi H, Svergun DI, Kursula P, Schultz C, McCarthy AA, Hart DJ, Wilmanns M Structure. 2016 Apr 20. pii: S0969-2126(16)30030-2. doi:, 10.1016/j.str.2016.03.020. PMID:27133022<ref>PMID:27133022</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2a2a" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Death-associated protein kinase 3D structures|Death-associated protein kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Kursula P]] | |||
[[Category: Kursula | [[Category: Wilmanns M]] | ||
[[Category: Wilmanns | |||