View source for 6qi8


==Truncated human R2TP complex, structure 3 (ADP-filled)==
<SX load='6qi8' size='340' side='right' viewer='molstar' caption='[[6qi8]], [[Resolution|resolution]] 3.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qi8]] is a 6 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=6QI8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QI8 FirstGlance]. <br>
</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RUVBL1, INO80H, NMP238, TIP49, TIP49A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RUVBL2, INO80J, TIP48, TIP49B, CGI-46 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></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=6qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qi8 OCA], [http://pdbe.org/6qi8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/6qi8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qi8 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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>  [[http://www.uniprot.org/uniprot/RUVB2_HUMAN RUVB2_HUMAN]] Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') 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: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: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:14966270</ref>   Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. May also inhibit the transcriptional activity of ATF2.<ref>PMID:14966270</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) is an HSP90 co-chaperone required for the maturation of several essential multiprotein complexes, including RNA polymerase II, small nucleolar ribonucleoproteins, and PIKK complexes such as mTORC1 and ATR-ATRIP. RUVBL1-RUVBL2 AAA-ATPases are also primary components of other essential complexes such as INO80 and Tip60 remodelers. Despite recent efforts, the molecular mechanisms regulating RUVBL1-RUVBL2 in these complexes remain elusive. Here, we report cryo-EM structures of R2TP and show how access to the nucleotide-binding site of RUVBL2 is coupled to binding of the client recruitment component of R2TP (PIH1D1) to its DII domain. This interaction induces conformational rearrangements that lead to the destabilization of an N-terminal segment of RUVBL2 that acts as a gatekeeper to nucleotide exchange. This mechanism couples protein-induced motions of the DII domains with accessibility of the nucleotide-binding site in RUVBL1-RUVBL2, and it is likely a general mechanism shared with other RUVBL1-RUVBL2-containing complexes.

Structural mechanism for regulation of the AAA-ATPases RUVBL1-RUVBL2 in the R2TP co-chaperone revealed by cryo-EM.,Munoz-Hernandez H, Pal M, Rodriguez CF, Fernandez-Leiro R, Prodromou C, Pearl LH, Llorca O Sci Adv. 2019 May 1;5(5):eaaw1616. doi: 10.1126/sciadv.aaw1616. eCollection 2019 , May. PMID:31049401<ref>PMID:31049401</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qi8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Helicase 3D structures|Helicase 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: DNA helicase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Llorca, O]]
[[Category: Munoz-Hernandez, H]]
[[Category: Rodriguez, C F]]
[[Category: Chaperone]]
[[Category: Cryo-em]]
[[Category: Hsp90 co-chaperone]]
[[Category: Pih1d1]]
[[Category: R2tp]]
[[Category: Rpap3]]
[[Category: Ruvbl1]]
[[Category: Ruvbl2]]