- EMDB-33126: Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 1:1 c... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-33126
タイトル
Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 1:1 complex
マップデータ
Dot1L, H2BK34ub
試料
複合体: Complex of Dot1L(1-416) and H2BK34ub 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-lysine N-methyltransferase, H3 lysine-79 specific
タンパク質・ペプチド: Histone domain-containing protein
DNA: DNA (146-MER)
DNA: DNA (146-MER)
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 / hypothalamus gonadotrophin-releasing hormone neuron development / female meiosis I / positive regulation of protein monoubiquitination / regulation of receptor signaling pathway via JAK-STAT / histone H3 methyltransferase activity / fat pad development ...[histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / histone H3K79 trimethyltransferase activity / regulation of transcription regulatory region DNA binding / hypothalamus gonadotrophin-releasing hormone neuron development / female meiosis I / positive regulation of protein monoubiquitination / regulation of receptor signaling pathway via JAK-STAT / histone H3 methyltransferase activity / fat pad development / mitochondrion transport along microtubule / histone methyltransferase activity / female gonad development / seminiferous tubule development / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / subtelomeric heterochromatin formation / Replacement of protamines by nucleosomes in the male pronucleus / Packaging Of Telomere Ends / energy homeostasis / regulation of neuron apoptotic process / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / regulation of proteasomal protein catabolic process / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / 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 / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / telomere organization / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Constitutive Signaling by NOTCH1 HD Domain Mutants / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / NOTCH2 Activation and Transmission of Signal to the Nucleus / Inhibition of DNA recombination at telomere / TICAM1,TRAF6-dependent induction of TAK1 complex / RNA Polymerase I Promoter Opening / Meiotic synapsis / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Regulation of FZD by ubiquitination / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / p75NTR recruits signalling complexes / Assembly of the ORC complex at the origin of replication / InlA-mediated entry of Listeria monocytogenes into host cells / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Regulation of pyruvate metabolism / Regulation of innate immune responses to cytosolic DNA / NF-kB is activated and signals survival / Downregulation of ERBB2:ERBB3 signaling / Pexophagy / NRIF signals cell death from the nucleus / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / VLDLR internalisation and degradation / Regulation of PTEN localization / DNA methylation / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Regulation of BACH1 activity / Condensation of Prophase Chromosomes / MAP3K8 (TPL2)-dependent MAPK1/3 activation / DNA damage checkpoint signaling / TICAM1, RIP1-mediated IKK complex recruitment / Chromatin modifications during the maternal to zygotic transition (MZT) / Translesion synthesis by REV1 / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Translesion synthesis by POLK / InlB-mediated entry of Listeria monocytogenes into host cell / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / Regulation of activated PAK-2p34 by proteasome mediated degradation / Translesion synthesis by POLI / PRC2 methylates histones and DNA / IKK complex recruitment mediated by RIP1 / innate immune response in mucosa / neuron projection morphogenesis / Gap-filling DNA repair synthesis and ligation in GG-NER / positive regulation of protein ubiquitination / PINK1-PRKN Mediated Mitophagy / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) 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.