View source for 2xsz


==The dodecameric human RuvBL1:RuvBL2 complex with truncated domains II==
<StructureSection load='2xsz' size='340' side='right'caption='[[2xsz]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xsz]] 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=2XSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XSZ 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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2xsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xsz OCA], [https://pdbe.org/2xsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xsz RCSB], [https://www.ebi.ac.uk/pdbsum/2xsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xsz 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> 
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== Publication Abstract from PubMed ==
RuvBL1 (RuvB-like 1) and its homolog RuvBL2 are evolutionarily highly conserved AAA(+) ATPases essential for many cellular activities. They play an important role in chromatin remodeling, transcriptional regulation and DNA damage repair. RuvBL1 and RuvBL2 are overexpressed in different types of cancer and interact with major oncogenic factors, such as beta-catenin and c-Myc regulating their function. We solved the first three-dimensional crystal structure of the human RuvBL complex with a truncated domain II and show that this complex is competent for helicase activity. The structure reveals a dodecamer consisting of two heterohexameric rings with alternating RuvBL1 and RuvBL2 monomers bound to ADP/ATP, that interact with each other via the retained part of domain II. The dodecameric quaternary structure of the R1DeltaDII/R2DeltaDII complex observed in the crystal structure was confirmed by small-angle X-ray scattering analysis. Interestingly, truncation of domain II led to a substantial increase in ATP consumption of RuvBL1, RuvBL2 and their complex. In addition, we present evidence that DNA unwinding of the human RuvBL proteins can be auto-inhibited by domain II, which is not present in the homologous bacterial helicase RuvB. Our data give new insights into the molecular arrangement of RuvBL1 and RuvBL2 and strongly suggest that in vivo activities of these highly interesting therapeutic drug targets are regulated by cofactors inducing conformational changes via domain II in order to modulate the enzyme complex into its active state.

Structural and functional insights into a dodecameric molecular machine - The RuvBL1/RuvBL2 complex.,Gorynia S, Bandeiras TM, Pinho FG, McVey CE, Vonrhein C, Round A, Svergun DI, Donner P, Matias PM, Carrondo MA J Struct Biol. 2011 Sep 10. PMID:21933716<ref>PMID:21933716</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2xsz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Helicase 3D structures|Helicase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bandeiras TM]]
[[Category: Carrondo MA]]
[[Category: Donner P]]
[[Category: Gorynia S]]
[[Category: Matias PM]]
[[Category: McVey CE]]
[[Category: Pinho FG]]
[[Category: Round A]]
[[Category: Svergun DI]]
[[Category: Vonrhein C]]