Complex: Bre1(mRBD-RING)/Rad6-Ub in complex with nucleosome
Protein or peptide: Histone H3.1
Protein or peptide: Histone H4
Protein or peptide: Histone H2A type 1-B/E
Protein or peptide: Histone H2B type 1-K
Protein or peptide: Histone H2B type 1-K
DNA: DNA (147-MER)
DNA: DNA (147-MER)
Protein or peptide: E3 ubiquitin-protein ligase BRE1
Protein or peptide: Ubiquitin-conjugating enzyme E2 2
Ligand: ZINC ION
Keywords
Nucleosome / Bre1 / Rad6 / Ub / NUCLEAR PROTEIN
Function / homology
Function and homology information
MUB1-RAD6-UBR2 ubiquitin ligase complex / RAD6-UBR2 ubiquitin ligase complex / sno(s)RNA transcription / Rad6-Rad18 complex / regulation of dipeptide transport / UBR1-RAD6 ubiquitin ligase complex / HULC complex / error-free postreplication DNA repair / stress-induced homeostatically regulated protein degradation pathway / ubiquitin-dependent protein catabolic process via the N-end rule pathway ...MUB1-RAD6-UBR2 ubiquitin ligase complex / RAD6-UBR2 ubiquitin ligase complex / sno(s)RNA transcription / Rad6-Rad18 complex / regulation of dipeptide transport / UBR1-RAD6 ubiquitin ligase complex / HULC complex / error-free postreplication DNA repair / stress-induced homeostatically regulated protein degradation pathway / ubiquitin-dependent protein catabolic process via the N-end rule pathway / meiotic DNA double-strand break formation / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / cytoplasm protein quality control by the ubiquitin-proteasome system / E3 ubiquitin ligases ubiquitinate target proteins / telomere maintenance via recombination / mitotic intra-S DNA damage checkpoint signaling / regulation of DNA-templated DNA replication initiation / DNA duplex unwinding / E2 ubiquitin-conjugating enzyme / error-free translesion synthesis / sporulation resulting in formation of a cellular spore / proteasome binding / mitotic G1 DNA damage checkpoint signaling / protein localization to CENP-A containing chromatin / DNA replication origin binding / ubiquitin conjugating enzyme activity / Antigen processing: Ubiquitination & Proteasome degradation / CENP-A containing nucleosome / subtelomeric heterochromatin formation / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends / cellular response to unfolded protein / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / error-prone translesion synthesis / telomere organization / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation / Deposition of new CENPA-containing nucleosomes at the centromere / hepoxilin biosynthetic process / ERAD pathway / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / linoleic acid metabolic process / Meiotic synapsis / Inhibition of DNA recombination at telomere / nucleosomal DNA binding / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / Interleukin-7 signaling / epigenetic regulation of gene expression / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Defective pyroptosis / Meiotic recombination / innate immune response in mucosa / DNA Damage/Telomere Stress Induced Senescence / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Transcriptional regulation of granulopoiesis / DNA-templated transcription termination / HDMs demethylate histones / Formation of the beta-catenin:TCF transactivating complex / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / double-strand break repair via homologous recombination / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / PKMTs methylate histone lysines / RING-type E3 ubiquitin transferase / B-WICH complex positively regulates rRNA expression / heterochromatin formation / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / Activation of anterior HOX genes in hindbrain development during early embryogenesis / structural constituent of chromatin / protein polyubiquitination / ubiquitin-protein transferase activity / UCH proteinases / nucleosome / ubiquitin protein ligase activity / antimicrobial humoral immune response mediated by antimicrobial peptide / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization Similarity search - Function
National Natural Science Foundation of China (NSFC)
22137005, 92253302, 22227810, 22277073, 92253302
China
Citation
Journal: Mol Cell / Year: 2023 Title: Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A. Authors: Zhiheng Deng / Huasong Ai / Maoshen Sun / Zebin Tong / Yunxiang Du / Qian Qu / Liying Zhang / Ziyu Xu / Shixian Tao / Qiang Shi / Jia-Bin Li / Man Pan / Lei Liu / Abstract: Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme ...Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme (yeast Rad6 or human hRAD6A), together, precisely deposit ubiquitin on H2B K123 in yeast or K120 in humans. Here, we developed a chemical trapping strategy and successfully captured the transient structures of Bre1- or RNF20/RNF40-mediated ubiquitin transfer from Rad6 or hRAD6A to nucleosomal H2B. Our structures show that Bre1 and RNF40 directly bind nucleosomal DNA, exhibiting a conserved E3/E2/nucleosome interaction pattern from yeast to humans for H2B monoubiquitylation. We also find an uncanonical non-hydrophobic contact in the Bre1 RING-Rad6 interface, which positions Rad6 directly above the target H2B lysine residue. Our study provides mechanistic insights into the site-specific monoubiquitylation of H2B, reveals a critical role of nucleosomal DNA in mediating E3 ligase recognition, and provides a framework for understanding the cancer-driving mutations of RNF20/RNF40.
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