登録情報 データベース : EMDB / ID : EMD-0695 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of human MLL1-NCP complex, binding mode2 マップデータMain map of human MLL1-NCP complex, binding mode2 詳細 試料複合体 : Human MLL1 complex associated with an unmodified nucleosome, binding mode 2複合体 : Human MLL1 complexタンパク質・ペプチド : x 8種DNA : x 2種複合体 : unmodified nucleosomeリガンド : x 2種 詳細 キーワード histone modification / nucleosome / MLL / TRANSCRIPTION / TRANSCRIPTION-DNA complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / Set1C/COMPASS complex ... protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / Set1C/COMPASS complex / MLL1/2 complex / T-helper 2 cell differentiation / definitive hemopoiesis / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / embryonic hemopoiesis / exploration behavior / anterior/posterior pattern specification / histone methyltransferase complex / regulation of tubulin deacetylation / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / regulation of embryonic development / hemopoiesis / MLL1 complex / transcription factor TFIID complex / RNA polymerase II general transcription initiation factor activity / histone acetyltransferase complex / negative regulation of fibroblast proliferation / homeostasis of number of cells within a tissue / positive regulation of gluconeogenesis / spleen development / transcription initiation-coupled chromatin remodeling / cellular response to transforming growth factor beta stimulus / methylated histone binding / 転移酵素; 一炭素原子の基を移すもの; メチル基を移すもの / post-embryonic development / skeletal system development / gluconeogenesis / Deactivation of the beta-catenin transactivating complex / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / euchromatin / lysine-acetylated histone binding / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / visual learning / protein modification process / mitotic spindle / PKMTs methylate histone lysines / beta-catenin binding / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / response to estrogen / structural constituent of chromatin / nucleosome / nucleosome assembly / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / HATs acetylate histones / histone binding / fibroblast proliferation / methylation / protein-containing complex assembly / transcription cis-regulatory region binding / regulation of cell cycle / protein heterodimerization activity / apoptotic process / DNA damage response / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / nucleolus / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / DNA binding / zinc ion binding / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol 類似検索 - 分子機能 : / ASH2, PHD zinc finger / Set1/Ash2 histone methyltransferase complex subunit ASH2-like, WH / Histone methyltransferase complex subunit ASH2 / Retinoblastoma-binding protein 5/Swd1 / KMT2A, ePHD domain / KMT2A, PHD domain 1 / KMT2A, PHD domain 2 / KMT2A, PHD domain 3 / Methyltransferase, trithorax ... : / ASH2, PHD zinc finger / Set1/Ash2 histone methyltransferase complex subunit ASH2-like, WH / Histone methyltransferase complex subunit ASH2 / Retinoblastoma-binding protein 5/Swd1 / KMT2A, ePHD domain / KMT2A, PHD domain 1 / KMT2A, PHD domain 2 / KMT2A, PHD domain 3 / Methyltransferase, trithorax / : / FY-rich, N-terminal / F/Y-rich N-terminus / PHD-like zinc-binding domain / FYR domain FYRN motif profile. / "FY-rich" domain, N-terminal region / FY-rich, C-terminal / F/Y rich C-terminus / FYR domain FYRC motif profile. / "FY-rich" domain, C-terminal region / CXXC zinc finger domain / Zinc finger, CXXC-type / Zinc finger CXXC-type profile. / Cysteine-rich motif following a subset of SET domains / Post-SET domain / Post-SET domain profile. / SPRY domain / B30.2/SPRY domain / B30.2/SPRY domain profile. / SPRY domain / B30.2/SPRY domain superfamily / Domain in SPla and the RYanodine Receptor. / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain / Extended PHD (ePHD) domain / Extended PHD (ePHD) domain profile. / SET domain profile. / SET domain / PHD-finger / Zinc finger PHD-type signature. / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site / Histone H2A signature. / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone H2A / Histone 2A / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Histone H3 signature 1. / Zinc finger, PHD-type / PHD zinc finger / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Zinc finger, FYVE/PHD-type / Histone-fold / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Concanavalin A-like lectin/glucanase domain superfamily / G-protein beta WD-40 repeat / Zinc finger, RING/FYVE/PHD-type / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily 類似検索 - ドメイン・相同性 Histone H3 / Histone H2B 1.1 / Histone H2A type 1 / WD repeat-containing protein 5 / Histone H4 / Histone H3.2 / Histone-lysine N-methyltransferase 2A / Retinoblastoma-binding protein 5 / Histone H2A / Set1/Ash2 histone methyltransferase complex subunit ASH2 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Xenopus laevis (アフリカツメガエル) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.5 Å 詳細 データ登録者Huang J / Xue H 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Science Foundation (China) 中国
引用ジャーナル : Nature / 年 : 2019タイトル : Structural basis of nucleosome recognition and modification by MLL methyltransferases.著者 : Han Xue / Tonghui Yao / Mi Cao / Guanjun Zhu / Yan Li / Guiyong Yuan / Yong Chen / Ming Lei / Jing Huang / 要旨 : Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and ... Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification. 履歴 登録 2019年7月20日 - ヘッダ(付随情報) 公開 2019年9月11日 - マップ公開 2019年9月11日 - 更新 2024年3月27日 - 現状 2024年3月27日 処理サイト : PDBj / 状態 : 公開
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