- EMDB-33127: Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 2:1 c... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-33127
タイトル
Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 2:1 complex
マップデータ
試料
複合体: Complex of Dot1L(1-416) and H2BK34ub 2:1 nucleosome
タンパク質・ペプチド: Ubiquitin
タンパク質・ペプチド: Histone H4
タンパク質・ペプチド: Histone H2A
タンパク質・ペプチド: Histone H2B type 1-K
タンパク質・ペプチド: Histone domain-containing protein
DNA: DNA (145-MER)
DNA: DNA (145-MER)
タンパク質・ペプチド: Histone-lysine N-methyltransferase, H3 lysine-79 specific
リガンド: S-ADENOSYLMETHIONINE
キーワード
Complex / Dot1L / H2BK34ub / Nucleosome / NUCLEAR PROTEIN
機能・相同性
機能・相同性情報
[histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / histone H3K79 trimethyltransferase activity / regulation of transcription regulatory region DNA binding / symbiont entry into host cell via disruption of host cell glycocalyx / regulation of receptor signaling pathway via JAK-STAT / histone H3 methyltransferase activity / symbiont entry into host cell via disruption of host cell envelope / histone methyltransferase activity / virus tail ...[histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / histone H3K79 trimethyltransferase activity / regulation of transcription regulatory region DNA binding / symbiont entry into host cell via disruption of host cell glycocalyx / regulation of receptor signaling pathway via JAK-STAT / histone H3 methyltransferase activity / symbiont entry into host cell via disruption of host cell envelope / histone methyltransferase activity / virus tail / subtelomeric heterochromatin formation / Replacement of protamines by nucleosomes in the male pronucleus / Packaging Of Telomere Ends / 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 / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / telomere organization / Inhibition of DNA recombination at telomere / RNA Polymerase I Promoter Opening / Meiotic synapsis / Assembly of the ORC complex at the origin of replication / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA damage checkpoint signaling / DNA methylation / Condensation of Prophase Chromosomes / Chromatin modifications during the maternal to zygotic transition (MZT) / SIRT1 negatively regulates rRNA expression / HCMV Late Events / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / innate immune response in mucosa / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / B-WICH complex positively regulates rRNA expression / PKMTs methylate histone lysines / Meiotic recombination / Pre-NOTCH Transcription and Translation / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / HCMV Early Events / antimicrobial humoral immune response mediated by antimicrobial peptide / structural constituent of chromatin / antibacterial humoral response / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / nucleosome / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Processing of DNA double-strand break ends / HATs acetylate histones / Senescence-Associated Secretory Phenotype (SASP) / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / Oxidative Stress Induced Senescence / defense response to Gram-negative bacterium / methylation / gene expression / Estrogen-dependent gene expression / killing of cells of another organism / nucleic acid binding / RNA polymerase II-specific DNA-binding transcription factor binding / transcription coactivator activity / chromosome, telomeric region / Ub-specific processing proteases / defense response to Gram-positive bacterium / Amyloid fiber formation / protein heterodimerization activity / DNA repair / intracellular membrane-bounded organelle / positive regulation of transcription by RNA polymerase II / protein-containing complex / extracellular space / DNA binding / nucleoplasm / nucleus / cytosol / cytoplasm 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
21977090
中国
National Natural Science Foundation of China (NSFC)
21532004
中国
National Natural Science Foundation of China (NSFC)
91753205
中国
National Natural Science Foundation of China (NSFC)
81621002
中国
引用
ジャーナル: Nat Chem Biol / 年: 2022 タイトル: H2B Lys34 Ubiquitination Induces Nucleosome Distortion to Stimulate Dot1L Activity. 著者: Huasong Ai / Maoshen Sun / Aijun Liu / Zixian Sun / Tingting Liu / Lin Cao / Lujun Liang / Qian Qu / Zichen Li / Zhiheng Deng / Zebin Tong / Guochao Chu / Xiaolin Tian / Haiteng Deng / Suwen ...著者: Huasong Ai / Maoshen Sun / Aijun Liu / Zixian Sun / Tingting Liu / Lin Cao / Lujun Liang / Qian Qu / Zichen Li / Zhiheng Deng / Zebin Tong / Guochao Chu / Xiaolin Tian / Haiteng Deng / Suwen Zhao / Jia-Bin Li / Zhiyong Lou / Lei Liu / 要旨: Ubiquitination-dependent histone crosstalk plays critical roles in chromatin-associated processes and is highly associated with human diseases. Mechanism studies of the crosstalk have been of the ...Ubiquitination-dependent histone crosstalk plays critical roles in chromatin-associated processes and is highly associated with human diseases. Mechanism studies of the crosstalk have been of the central focus. Here our study on the crosstalk between H2BK34ub and Dot1L-catalyzed H3K79me suggests a novel mechanism of ubiquitination-induced nucleosome distortion to stimulate the activity of an enzyme. We determined the cryo-electron microscopy structures of Dot1L-H2BK34ub nucleosome complex and the H2BK34ub nucleosome alone. The structures reveal that H2BK34ub induces an almost identical orientation and binding pattern of Dot1L on nucleosome as H2BK120ub, which positions Dot1L for the productive conformation through direct ubiquitin-enzyme contacts. However, H2BK34-anchored ubiquitin does not directly interact with Dot1L as occurs in the case of H2BK120ub, but rather induces DNA and histone distortion around the modified site. Our findings establish the structural framework for understanding the H2BK34ub-H3K79me trans-crosstalk and highlight the diversity of mechanisms for histone ubiquitination to activate chromatin-modifying enzymes.