5efq: Difference between revisions

Revision as of 06:56, 22 April 2020

Crystal structure of human Cdk13/Cyclin K in complex with ADP-aluminum fluoride

Structural highlights

5efq is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	ADP, AF3, MG
NonStd Res:	TPO
Gene:	CDK13, CDC2L, CDC2L5, CHED, KIAA1791 (HUMAN), CCNK, CPR4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CDK13_HUMAN] Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef.^[1] ^[2] ^[3] ^[4] [CCNK_HUMAN] May play a role in transcriptional regulation. In vitro, is associated with a kinase activity toward both RNA polymerase II C-terminal domain and CDK2 (CAK).^[5]

Publication Abstract from PubMed

Cyclin-dependent kinases regulate the cell cycle and transcription in higher eukaryotes. We have determined the crystal structure of the transcription kinase Cdk13 and its Cyclin K subunit at 2.0 A resolution. Cdk13 contains a C-terminal extension helix composed of a polybasic cluster and a DCHEL motif that interacts with the bound ATP. Cdk13/CycK phosphorylates both Ser5 and Ser2 of the RNA polymerase II C-terminal domain (CTD) with a preference for Ser7 pre-phosphorylations at a C-terminal position. The peptidyl-prolyl isomerase Pin1 does not change the phosphorylation specificities of Cdk9, Cdk12, and Cdk13 but interacts with the phosphorylated CTD through its WW domain. Using recombinant proteins, we find that flavopiridol inhibits Cdk7 more potently than it does Cdk13. Gene expression changes after knockdown of Cdk13 or Cdk12 are markedly different, with enrichment of growth signaling pathways for Cdk13-dependent genes. Together, our results provide insights into the structure, function, and activity of human Cdk13/CycK.

Structural and Functional Analysis of the Cdk13/Cyclin K Complex.,Greifenberg AK, Honig D, Pilarova K, Duster R, Bartholomeeusen K, Bosken CA, Anand K, Blazek D, Geyer M Cell Rep. 2016 Jan 12;14(2):320-31. doi: 10.1016/j.celrep.2015.12.025. Epub 2015 , Dec 31. PMID:26748711^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Even Y, Durieux S, Escande ML, Lozano JC, Peaucellier G, Weil D, Geneviere AM. CDC2L5, a Cdk-like kinase with RS domain, interacts with the ASF/SF2-associated protein p32 and affects splicing in vivo. J Cell Biochem. 2006 Oct 15;99(3):890-904. PMID:16721827 doi:https://dx.doi.org/10.1002/jcb.20986
↑ Lapidot-Lifson Y, Patinkin D, Prody CA, Ehrlich G, Seidman S, Ben-Aziz R, Benseler F, Eckstein F, Zakut H, Soreq H. Cloning and antisense oligodeoxynucleotide inhibition of a human homolog of cdc2 required in hematopoiesis. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):579-83. PMID:1731328
↑ Berro R, Pedati C, Kehn-Hall K, Wu W, Klase Z, Even Y, Geneviere AM, Ammosova T, Nekhai S, Kashanchi F. CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing. J Virol. 2008 Jul;82(14):7155-66. doi: 10.1128/JVI.02543-07. Epub 2008 May 14. PMID:18480452 doi:10.1128/JVI.02543-07
↑ Bartkowiak B, Liu P, Phatnani HP, Fuda NJ, Cooper JJ, Price DH, Adelman K, Lis JT, Greenleaf AL. CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev. 2010 Oct 15;24(20):2303-16. doi: 10.1101/gad.1968210. PMID:20952539 doi:https://dx.doi.org/10.1101/gad.1968210
↑ Fu TJ, Peng J, Lee G, Price DH, Flores O. Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription. J Biol Chem. 1999 Dec 3;274(49):34527-30. PMID:10574912
↑ Greifenberg AK, Honig D, Pilarova K, Duster R, Bartholomeeusen K, Bosken CA, Anand K, Blazek D, Geyer M. Structural and Functional Analysis of the Cdk13/Cyclin K Complex. Cell Rep. 2016 Jan 12;14(2):320-31. doi: 10.1016/j.celrep.2015.12.025. Epub 2015 , Dec 31. PMID:26748711 doi:https://dx.doi.org/10.1016/j.celrep.2015.12.025

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Even Y, Durieux S, Escande ML, Lozano JC, Peaucellier G, Weil D, Geneviere AM. CDC2L5, a Cdk-like kinase with RS domain, interacts with the ASF/SF2-associated protein p32 and affects splicing in vivo. J Cell Biochem. 2006 Oct 15;99(3):890-904. PMID:16721827 doi:https://dx.doi.org/10.1002/jcb.20986

[2] Lapidot-Lifson Y, Patinkin D, Prody CA, Ehrlich G, Seidman S, Ben-Aziz R, Benseler F, Eckstein F, Zakut H, Soreq H. Cloning and antisense oligodeoxynucleotide inhibition of a human homolog of cdc2 required in hematopoiesis. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):579-83. PMID:1731328

[3] Berro R, Pedati C, Kehn-Hall K, Wu W, Klase Z, Even Y, Geneviere AM, Ammosova T, Nekhai S, Kashanchi F. CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing. J Virol. 2008 Jul;82(14):7155-66. doi: 10.1128/JVI.02543-07. Epub 2008 May 14. PMID:18480452 doi:10.1128/JVI.02543-07

[4] Bartkowiak B, Liu P, Phatnani HP, Fuda NJ, Cooper JJ, Price DH, Adelman K, Lis JT, Greenleaf AL. CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev. 2010 Oct 15;24(20):2303-16. doi: 10.1101/gad.1968210. PMID:20952539 doi:https://dx.doi.org/10.1101/gad.1968210

[5] Fu TJ, Peng J, Lee G, Price DH, Flores O. Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription. J Biol Chem. 1999 Dec 3;274(49):34527-30. PMID:10574912

[6] Greifenberg AK, Honig D, Pilarova K, Duster R, Bartholomeeusen K, Bosken CA, Anand K, Blazek D, Geyer M. Structural and Functional Analysis of the Cdk13/Cyclin K Complex. Cell Rep. 2016 Jan 12;14(2):320-31. doi: 10.1016/j.celrep.2015.12.025. Epub 2015 , Dec 31. PMID:26748711 doi:https://dx.doi.org/10.1016/j.celrep.2015.12.025

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@@ Line 1: / Line 1: @@
 ==Crystal structure of human Cdk13/Cyclin K in complex with ADP-aluminum fluoride==
-<StructureSection load='5efq' size='340' side='right' caption='[[5efq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5efq' size='340' side='right'caption='[[5efq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5efq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EFQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EFQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5efq]] 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=5EFQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EFQ 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=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=5efq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efq OCA], [http://pdbe.org/5efq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efq RCSB], [http://www.ebi.ac.uk/pdbsum/5efq PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDK13, CDC2L, CDC2L5, CHED, KIAA1791 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCNK, CPR4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5efq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efq OCA], [http://pdbe.org/5efq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efq RCSB], [http://www.ebi.ac.uk/pdbsum/5efq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5efq ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 20: @@
 </div>
 <div class="pdbe-citations 5efq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cyclin 3D structures|Cyclin 3D structures]]
+*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Anand, K]]
 [[Category: Geyer, M]]

5efq: Difference between revisions

Revision as of 06:56, 22 April 2020

Crystal structure of human Cdk13/Cyclin K in complex with ADP-aluminum fluoride

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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