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'''Unreleased structure'''


The entry 6k0r is ON HOLD  until Paper Publication
==Ruvbl1-Ruvbl2 with truncated domain II in complex with phosphorylated Cordycepin==
<StructureSection load='6k0r' size='340' side='right'caption='[[6k0r]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6k0r]] is a 12 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=6K0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6K0R 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]] 2.502&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3AT:3-DEOXYADENOSINE-5-TRIPHOSPHATE'>3AT</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CU0:[(2~{R},3~{S},4~{S})-3,4-bis(oxidanyl)oxolan-2-yl]methyl+phosphono+hydrogen+phosphate'>CU0</scene>, <scene name='pdbligand=CUU:[(2~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-oxolan-2-yl]methyl+phosphono+hydrogen+phosphate'>CUU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6k0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6k0r OCA], [https://pdbe.org/6k0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6k0r RCSB], [https://www.ebi.ac.uk/pdbsum/6k0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6k0r ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RUVB1_HUMAN RUVB1_HUMAN] Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity.<ref>PMID:11027681</ref> <ref>PMID:14506706</ref> <ref>PMID:11080158</ref> <ref>PMID:14695187</ref> <ref>PMID:14966270</ref>  Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.<ref>PMID:11027681</ref> <ref>PMID:14506706</ref> <ref>PMID:11080158</ref> <ref>PMID:14695187</ref> <ref>PMID:14966270</ref>  Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.<ref>PMID:11027681</ref> <ref>PMID:14506706</ref> <ref>PMID:11080158</ref> <ref>PMID:14695187</ref> <ref>PMID:14966270</ref>  Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. Essential for cell proliferation.<ref>PMID:11027681</ref> <ref>PMID:14506706</ref> <ref>PMID:11080158</ref> <ref>PMID:14695187</ref> <ref>PMID:14966270</ref>  May be able to bind plasminogen at cell surface and enhance plasminogen activation.<ref>PMID:11027681</ref> <ref>PMID:14506706</ref> <ref>PMID:11080158</ref> <ref>PMID:14695187</ref> <ref>PMID:14966270</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Transcriptional regulation lies at the core of the circadian clockwork, but how the clock-related transcription machinery controls the circadian phase is not understood. Here, we show both in human cells and in mice that RuvB-like ATPase 2 (RUVBL2) interacts with other known clock proteins on chromatin to regulate the circadian phase. Pharmacological perturbation of RUVBL2 with the adenosine analog compound cordycepin resulted in a rapid-onset 12-hour clock phase-shift phenotype at human cell, mouse tissue, and whole-animal live imaging levels. Using simple peripheral injection treatment, we found that cordycepin penetrated the blood-brain barrier and caused rapid entrainment of the circadian phase, facilitating reduced duration of recovery in a mouse jet-lag model. We solved a crystal structure for human RUVBL2 in complex with a physiological metabolite of cordycepin, and biochemical assays showed that cordycepin treatment caused disassembly of an interaction between RUVBL2 and the core clock component BMAL1. Moreover, we showed with spike-in ChIP-seq analysis and binding assays that cordycepin treatment caused disassembly of the circadian super-complex, which normally resides at E-box chromatin loci such as PER1, PER2, DBP, and NR1D1 Mathematical modeling supported that the observed type 0 phase shifts resulted from derepression of E-box clock gene transcription.


Authors:  
Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals.,Ju D, Zhang W, Yan J, Zhao H, Li W, Wang J, Liao M, Xu Z, Wang Z, Zhou G, Mei L, Hou N, Ying S, Cai T, Chen S, Xie X, Lai L, Tang C, Park N, Takahashi JS, Huang N, Qi X, Zhang EE Sci Transl Med. 2020 May 6;12(542). pii: 12/542/eaba0769. doi:, 10.1126/scitranslmed.aba0769. PMID:32376767<ref>PMID:32376767</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 6k0r" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen L]]
[[Category: Huang N]]
[[Category: Ju D]]
[[Category: Li W]]
[[Category: Zhang E]]
[[Category: Zhang W]]

Latest revision as of 13:24, 22 November 2023

Ruvbl1-Ruvbl2 with truncated domain II in complex with phosphorylated CordycepinRuvbl1-Ruvbl2 with truncated domain II in complex with phosphorylated Cordycepin

Structural highlights

6k0r is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.502Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RUVB1_HUMAN Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity.[1] [2] [3] [4] [5] Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.[6] [7] [8] [9] [10] Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.[11] [12] [13] [14] [15] Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. Essential for cell proliferation.[16] [17] [18] [19] [20] May be able to bind plasminogen at cell surface and enhance plasminogen activation.[21] [22] [23] [24] [25]

Publication Abstract from PubMed

Transcriptional regulation lies at the core of the circadian clockwork, but how the clock-related transcription machinery controls the circadian phase is not understood. Here, we show both in human cells and in mice that RuvB-like ATPase 2 (RUVBL2) interacts with other known clock proteins on chromatin to regulate the circadian phase. Pharmacological perturbation of RUVBL2 with the adenosine analog compound cordycepin resulted in a rapid-onset 12-hour clock phase-shift phenotype at human cell, mouse tissue, and whole-animal live imaging levels. Using simple peripheral injection treatment, we found that cordycepin penetrated the blood-brain barrier and caused rapid entrainment of the circadian phase, facilitating reduced duration of recovery in a mouse jet-lag model. We solved a crystal structure for human RUVBL2 in complex with a physiological metabolite of cordycepin, and biochemical assays showed that cordycepin treatment caused disassembly of an interaction between RUVBL2 and the core clock component BMAL1. Moreover, we showed with spike-in ChIP-seq analysis and binding assays that cordycepin treatment caused disassembly of the circadian super-complex, which normally resides at E-box chromatin loci such as PER1, PER2, DBP, and NR1D1 Mathematical modeling supported that the observed type 0 phase shifts resulted from derepression of E-box clock gene transcription.

Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals.,Ju D, Zhang W, Yan J, Zhao H, Li W, Wang J, Liao M, Xu Z, Wang Z, Zhou G, Mei L, Hou N, Ying S, Cai T, Chen S, Xie X, Lai L, Tang C, Park N, Takahashi JS, Huang N, Qi X, Zhang EE Sci Transl Med. 2020 May 6;12(542). pii: 12/542/eaba0769. doi:, 10.1126/scitranslmed.aba0769. PMID:32376767[26]

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

References

  1. ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
  2. ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
  3. ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
  4. ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
  5. ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
  6. ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
  7. ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
  8. ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
  9. ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
  10. ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
  11. ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
  12. ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
  13. ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
  14. ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
  15. ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
  16. ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
  17. ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
  18. ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
  19. ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
  20. ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
  21. ↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
  22. ↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
  23. ↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
  24. ↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
  25. ↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
  26. ↑ Ju D, Zhang W, Yan J, Zhao H, Li W, Wang J, Liao M, Xu Z, Wang Z, Zhou G, Mei L, Hou N, Ying S, Cai T, Chen S, Xie X, Lai L, Tang C, Park N, Takahashi JS, Huang N, Qi X, Zhang EE. Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals. Sci Transl Med. 2020 May 6;12(542). pii: 12/542/eaba0769. doi:, 10.1126/scitranslmed.aba0769. PMID:32376767 doi:http://dx.doi.org/10.1126/scitranslmed.aba0769

6k0r, resolution 2.50Å

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