View source for 7lyc


==Cryo-EM structure of the human nucleosome core particle ubiquitylated at histone H2A Lys13 and Lys15 in complex with BARD1 (residues 415-777)==
<StructureSection load='7lyc' size='340' side='right'caption='[[7lyc]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lyc]] 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=7LYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LYC 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]] 2.94&#8491;</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=7lyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lyc OCA], [https://pdbe.org/7lyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lyc RCSB], [https://www.ebi.ac.uk/pdbsum/7lyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lyc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The BRCA1-BARD1 tumour suppressor is an E3 ubiquitin ligase necessary for the repair of DNA double-strand breaks by homologous recombination(1-10). The BRCA1-BARD1 complex localizes to damaged chromatin after DNA replication and catalyses the ubiquitylation of histone H2A and other cellular targets(11-14). The molecular bases for the recruitment to double-strand breaks and target recognition of BRCA1-BARD1 remain unknown. Here we use cryo-electron microscopy to show that the ankyrin repeat and tandem BRCT domains in BARD1 adopt a compact fold and bind to nucleosomal histones, DNA and monoubiquitin attached to H2A amino-terminal K13 or K15, two signals known to be specific for double-strand breaks(15,16). We further show that RING domains(17) in BRCA1-BARD1 orient an E2 ubiquitin-conjugating enzyme atop the nucleosome in a dynamic conformation, primed for ubiquitin transfer to the flexible carboxy-terminal tails of H2A and variant H2AX. Our work reveals a regulatory crosstalk in which recognition of monoubiquitin by BRCA1-BARD1 at the N terminus of H2A blocks the formation of polyubiquitin chains and cooperatively promotes ubiquitylation at the C terminus of H2A. These findings elucidate the mechanisms of BRCA1-BARD1 chromatin recruitment and ubiquitylation specificity, highlight key functions of BARD1 in both processes and explain how BRCA1-BARD1 promotes homologous recombination by opposing the DNA repair protein 53BP1 in post-replicative chromatin(18-22). These data provide a structural framework to evaluate BARD1 variants and help to identify mutations that drive the development of cancer.

Mechanisms of BRCA1-BARD1 nucleosome recognition and ubiquitylation.,Hu Q, Botuyan MV, Zhao D, Cui G, Mer E, Mer G Nature. 2021 Aug;596(7872):438-443. doi: 10.1038/s41586-021-03716-8. Epub 2021 , Jul 28. PMID:34321665<ref>PMID:34321665</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lyc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone 3D structures|Histone 3D structures]]
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Botuyan MV]]
[[Category: Cui D]]
[[Category: Hu Q]]
[[Category: Mer E]]
[[Category: Mer G]]
[[Category: Zhao D]]