[English] 日本語
![](img/lk-miru.gif)
- PDB-7jzv: Cryo-EM structure of the BRCA1-UbcH5c/BARD1 E3-E2 module bound to... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 7jzv | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the BRCA1-UbcH5c/BARD1 E3-E2 module bound to a nucleosome | ||||||
![]() |
| ||||||
![]() | LIGASE/DNA / Complex / Ubiquitin / Nucleosome / RING / ligase / LIGASE-DNA complex | ||||||
Function / homology | ![]() negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / random inactivation of X chromosome / negative regulation of centriole replication / sex-chromosome dosage compensation ...negative regulation of mRNA 3'-end processing / Defective DNA double strand break response due to BRCA1 loss of function / Defective DNA double strand break response due to BARD1 loss of function / BRCA1-BARD1 complex / BRCA1-C complex / BRCA1-B complex / BRCA1-A complex / random inactivation of X chromosome / negative regulation of centriole replication / sex-chromosome dosage compensation / negative regulation of intracellular estrogen receptor signaling pathway / gamma-tubulin ring complex / nuclear ubiquitin ligase complex / DNA strand resection involved in replication fork processing / chordate embryonic development / cellular response to indole-3-methanol / negative regulation of fatty acid biosynthetic process / (E3-independent) E2 ubiquitin-conjugating enzyme / homologous recombination / lateral element / tissue homeostasis / Signaling by BMP / protein K6-linked ubiquitination / regulation of DNA damage checkpoint / regulation of phosphorylation / protein K11-linked ubiquitination / Impaired BRCA2 binding to PALB2 / XY body / mitotic G2/M transition checkpoint / negative regulation of protein export from nucleus / postreplication repair / DNA repair complex / RNA polymerase binding / centrosome cycle / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / positive regulation of protein targeting to mitochondrion / Resolution of D-loop Structures through Holliday Junction Intermediates / negative regulation of gene expression via chromosomal CpG island methylation / intracellular non-membrane-bounded organelle / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / DNA-binding transcription activator activity / E2 ubiquitin-conjugating enzyme / response to ionizing radiation / Transcriptional Regulation by E2F6 / protein monoubiquitination / mitotic G2 DNA damage checkpoint signaling / ubiquitin conjugating enzyme activity / Presynaptic phase of homologous DNA pairing and strand exchange / negative regulation of cell cycle / negative regulation of BMP signaling pathway / positive regulation of vascular endothelial growth factor production / negative regulation of reactive oxygen species metabolic process / negative regulation of megakaryocyte differentiation / localization / protein localization to CENP-A containing chromatin / protein autoubiquitination / protein K48-linked ubiquitination / Chromatin modifying enzymes / regulation of DNA repair / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / SUMOylation of DNA damage response and repair proteins / heterochromatin organization / Packaging Of Telomere Ends / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / ubiquitin ligase complex / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / positive regulation of DNA repair / telomere organization / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / tubulin binding / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / TICAM1, RIP1-mediated IKK complex recruitment / DNA methylation / Condensation of Prophase Chromosomes / IKK complex recruitment mediated by RIP1 / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / PRC2 methylates histones and DNA / innate immune response in mucosa / male germ cell nucleus / Defective pyroptosis / chromosome segregation / Negative regulators of DDX58/IFIH1 signaling Similarity search - Function | ||||||
Biological species | ![]() synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||
![]() | Witus, S.R. / Burrell, A.L. / Hansen, J.M. / Farrell, D.P. / Dimaio, F. / Kollman, J.M. / Klevit, R.E. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: BRCA1/BARD1 site-specific ubiquitylation of nucleosomal H2A is directed by BARD1. Authors: Samuel R Witus / Anika L Burrell / Daniel P Farrell / Jianming Kang / Meiling Wang / Jesse M Hansen / Alex Pravat / Lisa M Tuttle / Mikaela D Stewart / Peter S Brzovic / Champak Chatterjee / ...Authors: Samuel R Witus / Anika L Burrell / Daniel P Farrell / Jianming Kang / Meiling Wang / Jesse M Hansen / Alex Pravat / Lisa M Tuttle / Mikaela D Stewart / Peter S Brzovic / Champak Chatterjee / Weixing Zhao / Frank DiMaio / Justin M Kollman / Rachel E Klevit / ![]() Abstract: Mutations in the E3 ubiquitin ligase RING domains of BRCA1/BARD1 predispose carriers to breast and ovarian cancers. We present the structure of the BRCA1/BARD1 RING heterodimer with the E2 enzyme ...Mutations in the E3 ubiquitin ligase RING domains of BRCA1/BARD1 predispose carriers to breast and ovarian cancers. We present the structure of the BRCA1/BARD1 RING heterodimer with the E2 enzyme UbcH5c bound to its cellular target, the nucleosome, along with biochemical data that explain how the complex selectively ubiquitylates lysines 125, 127 and 129 in the flexible C-terminal tail of H2A in a fully human system. The structure reveals that a novel BARD1-histone interface couples to a repositioning of UbcH5c compared to the structurally similar PRC1 E3 ligase Ring1b/Bmi1 that ubiquitylates H2A Lys119 in nucleosomes. This interface is sensitive to both H3 Lys79 methylation status and mutations found in individuals with cancer. Furthermore, NMR reveals an unexpected mode of E3-mediated substrate regulation through modulation of dynamics in the C-terminal tail of H2A. Our findings provide insight into how E3 ligases preferentially target nearby lysine residues in nucleosomes by a steric occlusion and distancing mechanism. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 335.1 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 245.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.6 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 46.1 KB | Display | |
Data in CIF | ![]() | 72.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 22581MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |