View source for 8juz


==Human ATAD2 Walker B mutant-H3/H4K5Q complex, ATP state (Class III)==
<StructureSection load='8juz' size='340' side='right'caption='[[8juz]], [[Resolution|resolution]] 4.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8juz]] 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=8JUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JUZ 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]] 4.29&#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=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</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=8juz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8juz OCA], [https://pdbe.org/8juz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8juz RCSB], [https://www.ebi.ac.uk/pdbsum/8juz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8juz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATAD2_HUMAN ATAD2_HUMAN] May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells.<ref>PMID:17998543</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ATAD2 is a non-canonical ATP-dependent histone chaperone and a major cancer target. Despite widespread efforts to design drugs targeting the ATAD2 bromodomain, little is known about the overall structural organization and regulation of ATAD2. Here, we present the 3.1 A cryo-EM structure of human ATAD2 in the ATP state, showing a shallow hexameric spiral that binds a peptide substrate at the central pore. The spiral conformation is locked by an N-terminal linker domain (LD) that wedges between the seam subunits, thus limiting ATP-dependent symmetry breaking of the AAA+ ring. In contrast, structures of the ATAD2-histone H3/H4 complex show the LD undocked from the seam, suggesting that H3/H4 binding unlocks the AAA+ spiral by allosterically releasing the LD. These findings, together with the discovery of an inter-subunit signaling mechanism, reveal a unique regulatory mechanism for ATAD2 and lay the foundation for developing new ATAD2 inhibitors.

Structure of the human ATAD2 AAA+ histone chaperone reveals mechanism of regulation and inter-subunit communication.,Cho C, Ganser C, Uchihashi T, Kato K, Song JJ Commun Biol. 2023 Sep 28;6(1):993. doi: 10.1038/s42003-023-05373-1. PMID:37770645<ref>PMID:37770645</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8juz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cho C]]
[[Category: Song J]]