1g3n

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[[Image:1g3n.jpg|left|200px]]
 
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==STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX==
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The line below this paragraph, containing "STRUCTURE_1g3n", creates the "Structure Box" on the page.
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<StructureSection load='1g3n' size='340' side='right'caption='[[1g3n]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1g3n]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G3N FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1g3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g3n OCA], [https://pdbe.org/1g3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g3n RCSB], [https://www.ebi.ac.uk/pdbsum/1g3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g3n ProSAT]</span></td></tr>
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{{STRUCTURE_1g3n| PDB=1g3n | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CDK6_HUMAN CDK6_HUMAN] Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans.<ref>PMID:8114739</ref> <ref>PMID:12833137</ref> <ref>PMID:14985467</ref> <ref>PMID:15254224</ref> <ref>PMID:15809340</ref> <ref>PMID:17431401</ref> <ref>PMID:17420273</ref> <ref>PMID:20668294</ref> <ref>PMID:20333249</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g3/1g3n_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1g3n ConSurf].
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<div style="clear:both"></div>
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'''STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX'''
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==See Also==
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*[[Cyclin 3D structures|Cyclin 3D structures]]
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*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
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==Overview==
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== References ==
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The cyclin-dependent kinases 4 and 6 (Cdk4/6) that drive progression through the G(1) phase of the cell cycle play a central role in the control of cell proliferation, and CDK deregulation is a frequent event in cancer. Cdk4/6 are regulated by the D-type cyclins, which bind to CDKs and activate the kinase, and by the INK4 family of inhibitors. INK4 proteins can bind both monomeric CDK, preventing its association with a cyclin, and also the CDK-cyclin complex, forming an inactive ternary complex. In vivo, binary INK4-Cdk4/6 complexes are more abundant than ternary INK4-Cdk4/6-cyclinD complexes, and it has been suggested that INK4 binding may lead to the eventual dissociation of the cyclin. Here we present the 2.9-A crystal structure of the inactive ternary complex between Cdk6, the INK4 inhibitor p18(INK4c), and a D-type viral cyclin. The structure reveals that p18(INK4c) inhibits the CDK-cyclin complex by distorting the ATP binding site and misaligning catalytic residues. p18(INK4c) also distorts the cyclin-binding site, with the cyclin remaining bound at an interface that is substantially reduced in size. These observations support the model that INK4 binding weakens the cyclin's affinity for the CDK. This structure also provides insights into the specificity of the D-type cyclins for Cdk4/6.
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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1G3N is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_herpesvirus_8 Human herpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G3N OCA].
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==Reference==
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Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors., Jeffrey PD, Tong L, Pavletich NP, Genes Dev. 2000 Dec 15;14(24):3115-25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11124804 11124804]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Human herpesvirus 8]]
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[[Category: Human gammaherpesvirus 8]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Jeffrey PD]]
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[[Category: Jeffrey, P D.]]
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[[Category: Pavletich NP]]
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[[Category: Pavletich, N P.]]
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[[Category: Tong L]]
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[[Category: Tong, L.]]
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[[Category: Cyclin-dependent kinase]]
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[[Category: Ink4 inhibitor]]
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[[Category: Viral cyclin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:05:48 2008''
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Current revision

STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX

PDB ID 1g3n

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