7lyc: Difference between revisions
New page: '''Unreleased structure''' The entry 7lyc is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==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]] 2.94Å' 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]] 2.94Å</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </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]] | |||
Latest revision as of 12:28, 9 October 2024
Cryo-EM structure of the human nucleosome core particle ubiquitylated at histone H2A Lys13 and Lys15 in complex with BARD1 (residues 415-777)Cryo-EM structure of the human nucleosome core particle ubiquitylated at histone H2A Lys13 and Lys15 in complex with BARD1 (residues 415-777)
Structural highlights
Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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