7p6x
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Cryo-Em structure of the hexameric RUVBL1-RUVBL2 in complex with ZNHIT2== |
| - | <StructureSection load='7p6x' size='340' side='right'caption='[[7p6x]]' scene=''> | + | <StructureSection load='7p6x' size='340' side='right'caption='[[7p6x]], [[Resolution|resolution]] 4.10Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7p6x]] is a 6 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=7P6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P6X FirstGlance]. <br> |
| - | </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=7p6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p6x OCA], [https://pdbe.org/7p6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p6x RCSB], [https://www.ebi.ac.uk/pdbsum/7p6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p6x ProSAT]</span></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></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=7p6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p6x OCA], [https://pdbe.org/7p6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p6x RCSB], [https://www.ebi.ac.uk/pdbsum/7p6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p6x ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Biogenesis of the U5 small nuclear ribonucleoprotein (snRNP) is an essential and highly regulated process. In particular, PRPF8, one of U5 snRNP main components, requires HSP90 working in concert with R2TP, a cochaperone complex containing RUVBL1 and RUVBL2 AAA-ATPases, and additional factors that are still poorly characterized. Here, we use biochemistry, interaction mapping, mass spectrometry and cryoEM to study the role of ZNHIT2 in the regulation of the R2TP chaperone during the biogenesis of PRPF8. ZNHIT2 forms a complex with R2TP which depends exclusively on the direct interaction of ZNHIT2 with the RUVBL1-RUVBL2 ATPases. The cryoEM analysis of this complex reveals that ZNHIT2 alters the conformation and nucleotide state of RUVBL1-RUVBL2, affecting its ATPase activity. We characterized the interactions between R2TP, PRPF8, ZNHIT2, ECD and AAR2 proteins. Interestingly, PRPF8 makes a direct interaction with R2TP and this complex can incorporate ZNHIT2 and other proteins involved in the biogenesis of PRPF8 such as ECD and AAR2. Together, these results show that ZNHIT2 participates in the assembly of the U5 snRNP as part of a network of contacts between assembly factors required for PRPF8 biogenesis and the R2TP-HSP90 chaperone, while concomitantly regulating the structure and nucleotide state of R2TP. | ||
| + | |||
| + | CryoEM of RUVBL1-RUVBL2-ZNHIT2, a complex that interacts with pre-mRNA-processing-splicing factor 8.,Serna M, Gonzalez-Corpas A, Cabezudo S, Lopez-Perrote A, Degliesposti G, Zarzuela E, Skehel JM, Munoz J, Llorca O Nucleic Acids Res. 2022 Jan 25;50(2):1128-1146. doi: 10.1093/nar/gkab1267. PMID:34951455<ref>PMID:34951455</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7p6x" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Fernandez-Leiro R]] |
| + | [[Category: Llorca O]] | ||
| + | [[Category: Serna M]] | ||
Revision as of 06:53, 25 January 2023
Cryo-Em structure of the hexameric RUVBL1-RUVBL2 in complex with ZNHIT2
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