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| | ==Structural mechanism of Nek7 activation by Nek9-induced dimerisation== | | ==Structural mechanism of Nek7 activation by Nek9-induced dimerisation== |
| - | <StructureSection load='5de2' size='340' side='right' caption='[[5de2]], [[Resolution|resolution]] 2.78Å' scene=''> | + | <StructureSection load='5de2' size='340' side='right'caption='[[5de2]], [[Resolution|resolution]] 2.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5de2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DE2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DE2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5de2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DE2 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wqm|2wqm]], [[2wqn|2wqn]]</td></tr> | + | </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=5de2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5de2 OCA], [https://pdbe.org/5de2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5de2 RCSB], [https://www.ebi.ac.uk/pdbsum/5de2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5de2 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NEK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=5de2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5de2 OCA], [http://pdbe.org/5de2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5de2 RCSB], [http://www.ebi.ac.uk/pdbsum/5de2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5de2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NEK7_HUMAN NEK7_HUMAN]] Protein kinase which plays an important role in mitotic cell cycle progression. Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis. Phosphorylates RPS6KB1.<ref>PMID:17101132</ref> <ref>PMID:17586473</ref> <ref>PMID:19414596</ref> [[http://www.uniprot.org/uniprot/NEK9_MOUSE NEK9_MOUSE]] Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation. Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2. Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues Important for G1/S transition and S phase progression. Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively (By similarity). | + | [https://www.uniprot.org/uniprot/NEK7_HUMAN NEK7_HUMAN] Protein kinase which plays an important role in mitotic cell cycle progression. Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis. Phosphorylates RPS6KB1.<ref>PMID:17101132</ref> <ref>PMID:17586473</ref> <ref>PMID:19414596</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5de2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5de2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bayliss, R]] | + | [[Category: Mus musculus]] |
| - | [[Category: Haq, T]] | + | [[Category: Bayliss R]] |
| - | [[Category: Mitosis]] | + | [[Category: Haq T]] |
| - | [[Category: Protein kinase]]
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| - | [[Category: Protein-protein interaction]]
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| - | [[Category: Transferase]]
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| Structural highlights
Function
NEK7_HUMAN Protein kinase which plays an important role in mitotic cell cycle progression. Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis. Phosphorylates RPS6KB1.[1] [2] [3]
Publication Abstract from PubMed
Mitotic spindle assembly requires the regulated activities of protein kinases such as Nek7 and Nek9. Nek7 is autoinhibited by the protrusion of Tyr97 into the active site and activated by the Nek9 non-catalytic C-terminal domain (CTD). CTD binding apparently releases autoinhibition because mutation of Tyr97 to phenylalanine increases Nek7 activity independently of Nek9. Here we find that self-association of the Nek9-CTD is needed for Nek7 activation. We map the minimal Nek7 binding region of Nek9 to residues 810-828. A crystal structure of Nek7(Y97F) bound to Nek9(810-828) reveals a binding site on the C-lobe of the Nek7 kinase domain. Nek7(Y97F) crystallizes as a back-to-back dimer between kinase domain N-lobes, in which the specific contacts within the interface are coupled to the conformation of residue 97. Hence, we propose that the Nek9-CTD activates Nek7 through promoting back-to-back dimerization that releases the autoinhibitory tyrosine residue, a mechanism conserved in unrelated kinase families.
Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization.,Haq T, Richards MW, Burgess SG, Gallego P, Yeoh S, O'Regan L, Reverter D, Roig J, Fry AM, Bayliss R Nat Commun. 2015 Nov 2;6:8771. doi: 10.1038/ncomms9771. PMID:26522158[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yissachar N, Salem H, Tennenbaum T, Motro B. Nek7 kinase is enriched at the centrosome, and is required for proper spindle assembly and mitotic progression. FEBS Lett. 2006 Nov 27;580(27):6489-95. Epub 2006 Nov 7. PMID:17101132 doi:http://dx.doi.org/10.1016/j.febslet.2006.10.069
- ↑ Kim S, Lee K, Rhee K. NEK7 is a centrosomal kinase critical for microtubule nucleation. Biochem Biophys Res Commun. 2007 Aug 17;360(1):56-62. Epub 2007 Jun 8. PMID:17586473 doi:http://dx.doi.org/10.1016/j.bbrc.2007.05.206
- ↑ O'Regan L, Fry AM. The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis. Mol Cell Biol. 2009 Jul;29(14):3975-90. doi: 10.1128/MCB.01867-08. Epub 2009 May , 4. PMID:19414596 doi:http://dx.doi.org/10.1128/MCB.01867-08
- ↑ Haq T, Richards MW, Burgess SG, Gallego P, Yeoh S, O'Regan L, Reverter D, Roig J, Fry AM, Bayliss R. Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization. Nat Commun. 2015 Nov 2;6:8771. doi: 10.1038/ncomms9771. PMID:26522158 doi:http://dx.doi.org/10.1038/ncomms9771
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