4aaa: Difference between revisions
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==Crystal structure of the human CDKL2 kinase domain== | |||
<StructureSection load='4aaa' size='340' side='right'caption='[[4aaa]], [[Resolution|resolution]] 1.53Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aaa]] is a 1 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=4AAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AAA 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]] 1.53Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DKI:5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE'>DKI</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4aaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aaa OCA], [https://pdbe.org/4aaa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aaa RCSB], [https://www.ebi.ac.uk/pdbsum/4aaa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aaa ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CDKL2_HUMAN CDKL2_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Various kinases, including a cyclin-dependent kinase (CDK) family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL) proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs), including an unusual ?J helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1-4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and ?J helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy. | |||
CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.,Canning P, Park K, Goncalves J, Li C, Howard CJ, Sharpe TD, Holt LJ, Pelletier L, Bullock AN, Leroux MR Cell Rep. 2018 Jan 23;22(4):885-894. doi: 10.1016/j.celrep.2017.12.083. Epub 2018, Jan 28. PMID:29420175<ref>PMID:29420175</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4aaa" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Arrowsmith CH]] | |||
[[Category: Berridge G]] | |||
[[Category: Bountra C]] | |||
[[Category: Bullock A]] | |||
[[Category: Burgess-Brown N]] | |||
[[Category: Canning P]] | |||
[[Category: Cooper CDO]] | |||
[[Category: Daga N]] | |||
[[Category: Edwards AM]] | |||
[[Category: Krojer T]] | |||
[[Category: Mahajan P]] | |||
[[Category: Muniz JRC]] | |||
[[Category: Vollmar M]] | |||
[[Category: Weigelt J]] | |||
[[Category: Von Delft F]] | |||
Latest revision as of 14:22, 20 December 2023
Crystal structure of the human CDKL2 kinase domainCrystal structure of the human CDKL2 kinase domain
Structural highlights
FunctionPublication Abstract from PubMedVarious kinases, including a cyclin-dependent kinase (CDK) family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL) proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs), including an unusual ?J helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1-4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and ?J helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy. CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.,Canning P, Park K, Goncalves J, Li C, Howard CJ, Sharpe TD, Holt LJ, Pelletier L, Bullock AN, Leroux MR Cell Rep. 2018 Jan 23;22(4):885-894. doi: 10.1016/j.celrep.2017.12.083. Epub 2018, Jan 28. PMID:29420175[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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