9er2: Difference between revisions

Latest revision as of 06:21, 4 December 2024

PolII-TCR-STK19 structure.

Structural highlights

9er2 is a 10 chain structure with sequence from Homo sapiens and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.3Å
Ligands:	ADP, BEF, MG, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

STK19_HUMAN Inactive serine/threonine-protein kinase (Probable) (PubMed:32531245, PubMed:32531246). May control NRAS activity via an associated kinase (Probable) (PubMed:32531246).^[1] ^[2] Inactive serine/threonine-protein kinase.^[3]

Publication Abstract from PubMed

Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and transcription factor IIH (TFIIH) around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryoelectron microscopy (cryo-EM) and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.

STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair.,van den Heuvel D, Rodriguez-Martinez M, van der Meer PJ, Nieto Moreno N, Park J, Kim HS, van Schie JJM, Wondergem AP, D'Souza A, Yakoub G, Herlihy AE, Kashyap K, Boissiere T, Walker J, Mitter R, Apelt K, de Lint K, Kirdok I, Ljungman M, Wolthuis RMF, Cramer P, Scharer OD, Kokic G, Svejstrup JQ, Luijsterburg MS Cell. 2024 Nov 11:S0092-8674(24)01200-5. doi: 10.1016/j.cell.2024.10.018. PMID:39547229^[4]

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

References

↑ Rodríguez-Martínez M, Boissiére T, Noe Gonzalez M, Litchfield K, Mitter R, Walker J, Kjœr S, Ismail M, Downward J, Swanton C, Svejstrup JQ. Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver. Cell. 2020 Jun 11;181(6):1395-1405.e11. PMID:32531245 doi:10.1016/j.cell.2020.04.014
↑ Yin C, Zhu B, Li X, Goding CR, Cui R. A Reply to ''Evidence that STK19 Is Not an NRAS-Dependent Melanoma Driver". Cell. 2020 Jun 11;181(6):1406-1409.e2. PMID:32531246 doi:10.1016/j.cell.2020.04.029
↑ Rodríguez-Martínez M, Boissiére T, Noe Gonzalez M, Litchfield K, Mitter R, Walker J, Kjœr S, Ismail M, Downward J, Swanton C, Svejstrup JQ. Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver. Cell. 2020 Jun 11;181(6):1395-1405.e11. PMID:32531245 doi:10.1016/j.cell.2020.04.014
↑ van den Heuvel D, Rodríguez-Martínez M, van der Meer PJ, Nieto Moreno N, Park J, Kim HS, van Schie JJM, Wondergem AP, D'Souza A, Yakoub G, Herlihy AE, Kashyap K, Boissière T, Walker J, Mitter R, Apelt K, de Lint K, Kirdök I, Ljungman M, Wolthuis RMF, Cramer P, Schärer OD, Kokic G, Svejstrup JQ, Luijsterburg MS. STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair. Cell. 2024 Nov 11:S0092-8674(24)01200-5. PMID:39547229 doi:10.1016/j.cell.2024.10.018

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OCA

[1] Rodríguez-Martínez M, Boissiére T, Noe Gonzalez M, Litchfield K, Mitter R, Walker J, Kjœr S, Ismail M, Downward J, Swanton C, Svejstrup JQ. Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver. Cell. 2020 Jun 11;181(6):1395-1405.e11. PMID:32531245 doi:10.1016/j.cell.2020.04.014

[2] Yin C, Zhu B, Li X, Goding CR, Cui R. A Reply to ''Evidence that STK19 Is Not an NRAS-Dependent Melanoma Driver". Cell. 2020 Jun 11;181(6):1406-1409.e2. PMID:32531246 doi:10.1016/j.cell.2020.04.029

[3] Rodríguez-Martínez M, Boissiére T, Noe Gonzalez M, Litchfield K, Mitter R, Walker J, Kjœr S, Ismail M, Downward J, Swanton C, Svejstrup JQ. Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver. Cell. 2020 Jun 11;181(6):1395-1405.e11. PMID:32531245 doi:10.1016/j.cell.2020.04.014

[4] van den Heuvel D, Rodríguez-Martínez M, van der Meer PJ, Nieto Moreno N, Park J, Kim HS, van Schie JJM, Wondergem AP, D'Souza A, Yakoub G, Herlihy AE, Kashyap K, Boissière T, Walker J, Mitter R, Apelt K, de Lint K, Kirdök I, Ljungman M, Wolthuis RMF, Cramer P, Schärer OD, Kokic G, Svejstrup JQ, Luijsterburg MS. STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair. Cell. 2024 Nov 11:S0092-8674(24)01200-5. PMID:39547229 doi:10.1016/j.cell.2024.10.018

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9er2 is ON HOLD  until Paper Publication
+==PolII-TCR-STK19 structure.==
+<StructureSection load='9er2' size='340' side='right'caption='[[9er2]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9er2]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ER2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ER2 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</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=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9er2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9er2 OCA], [https://pdbe.org/9er2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9er2 RCSB], [https://www.ebi.ac.uk/pdbsum/9er2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9er2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/STK19_HUMAN STK19_HUMAN] Inactive serine/threonine-protein kinase (Probable) (PubMed:32531245, PubMed:32531246). May control NRAS activity via an associated kinase (Probable) (PubMed:32531246).<ref>PMID:32531245</ref> <ref>PMID:32531246</ref>   Inactive serine/threonine-protein kinase.<ref>PMID:32531245</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and transcription factor IIH (TFIIH) around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryoelectron microscopy (cryo-EM) and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.
-Authors:
+STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair.,van den Heuvel D, Rodriguez-Martinez M, van der Meer PJ, Nieto Moreno N, Park J, Kim HS, van Schie JJM, Wondergem AP, D'Souza A, Yakoub G, Herlihy AE, Kashyap K, Boissiere T, Walker J, Mitter R, Apelt K, de Lint K, Kirdok I, Ljungman M, Wolthuis RMF, Cramer P, Scharer OD, Kokic G, Svejstrup JQ, Luijsterburg MS Cell. 2024 Nov 11:S0092-8674(24)01200-5. doi: 10.1016/j.cell.2024.10.018. PMID:39547229<ref>PMID:39547229</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9er2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Sus scrofa]]
+[[Category: Kokic G]]

9er2: Difference between revisions

Latest revision as of 06:21, 4 December 2024

PolII-TCR-STK19 structure.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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