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基本情報
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タイトル | The cryo-EM structure of human C complex | |||||||||
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![]() | spliceosome / RNA splicing / PRP16 / branching / SPLICING | |||||||||
機能・相同性 | ![]() striated muscle dense body / exon-exon junction subcomplex mago-y14 / negative regulation of selenocysteine incorporation / regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / post-spliceosomal complex / cellular response to selenite ion / exon-exon junction complex / selenocysteine insertion sequence binding / regulation of translation at postsynapse, modulating synaptic transmission / post-mRNA release spliceosomal complex ...striated muscle dense body / exon-exon junction subcomplex mago-y14 / negative regulation of selenocysteine incorporation / regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / post-spliceosomal complex / cellular response to selenite ion / exon-exon junction complex / selenocysteine insertion sequence binding / regulation of translation at postsynapse, modulating synaptic transmission / post-mRNA release spliceosomal complex / regulation of retinoic acid receptor signaling pathway / 3'-5' RNA helicase activity / negative regulation of excitatory postsynaptic potential / U2 snRNP binding / intracellular mRNA localization / U7 snRNA binding / histone pre-mRNA DCP binding / U7 snRNP / generation of catalytic spliceosome for first transesterification step / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / regulation of vitamin D receptor signaling pathway / histone pre-mRNA 3'end processing complex / cis assembly of pre-catalytic spliceosome / regulation of mRNA processing / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / Deadenylation of mRNA / embryonic brain development / spliceosome conformational change to release U4 (or U4atac) and U1 (or U11) / protein methylation / U12-type spliceosomal complex / methylosome / nuclear retinoic acid receptor binding / 7-methylguanosine cap hypermethylation / M-decay: degradation of maternal mRNAs by maternally stored factors / Prp19 complex / positive regulation of androgen receptor activity / poly(A) binding / snRNP binding / U1 snRNP binding / mRNA 3'-end processing / embryonic cranial skeleton morphogenesis / pICln-Sm protein complex / RNA splicing, via transesterification reactions / small nuclear ribonucleoprotein complex / pre-mRNA binding / U2-type catalytic step 1 spliceosome / sno(s)RNA-containing ribonucleoprotein complex / C2H2 zinc finger domain binding / regulation of mRNA splicing, via spliceosome / SMN-Sm protein complex / spliceosomal tri-snRNP complex / P granule / telomerase holoenzyme complex / mRNA cis splicing, via spliceosome / positive regulation by host of viral transcription / telomerase RNA binding / U2-type precatalytic spliceosome / U2-type spliceosomal complex / Transport of Mature mRNA derived from an Intron-Containing Transcript / commitment complex / positive regulation of vitamin D receptor signaling pathway / nuclear vitamin D receptor binding / U2-type prespliceosome assembly / U2-type catalytic step 2 spliceosome / Notch binding / positive regulation of mRNA splicing, via spliceosome / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / U4 snRNP / RUNX3 regulates NOTCH signaling / U2 snRNP / RNA Polymerase II Transcription Termination / NOTCH4 Intracellular Domain Regulates Transcription / exploration behavior / muscle organ development / U1 snRNP / ubiquitin-ubiquitin ligase activity / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / NOTCH3 Intracellular Domain Regulates Transcription / WD40-repeat domain binding / lipid biosynthetic process / Cajal body / positive regulation of neurogenesis / U2-type prespliceosome / cyclosporin A binding / nuclear androgen receptor binding / regulation of alternative mRNA splicing, via spliceosome / K63-linked polyubiquitin modification-dependent protein binding / positive regulation of G1/S transition of mitotic cell cycle / precatalytic spliceosome / retinoic acid receptor signaling pathway / Notch-HLH transcription pathway / generation of catalytic spliceosome for second transesterification step / positive regulation of transforming growth factor beta receptor signaling pathway / Formation of paraxial mesoderm / spliceosomal complex assembly / mRNA Splicing - Minor Pathway / SMAD binding / mitotic G2 DNA damage checkpoint signaling / associative learning 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.4 Å | |||||||||
![]() | Zhan X / Lu Y / Shi Y | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Molecular basis for the activation of human spliceosome. 著者: Xiechao Zhan / Yichen Lu / Yigong Shi / ![]() 要旨: The spliceosome executes pre-mRNA splicing through four sequential stages: assembly, activation, catalysis, and disassembly. Activation of the spliceosome, namely remodeling of the pre-catalytic ...The spliceosome executes pre-mRNA splicing through four sequential stages: assembly, activation, catalysis, and disassembly. Activation of the spliceosome, namely remodeling of the pre-catalytic spliceosome (B complex) into the activated spliceosome (B complex) and the catalytically activated spliceosome (B complex), involves major flux of protein components and structural rearrangements. Relying on a splicing inhibitor, we have captured six intermediate states between the B and B complexes: pre-B, B-I, B-II, B-III, B-IV, and post-B. Their cryo-EM structures, together with an improved structure of the catalytic step I spliceosome (C complex), reveal how the catalytic center matures around the internal stem loop of U6 snRNA, how the branch site approaches 5'-splice site, how the RNA helicase PRP2 rearranges to bind pre-mRNA, and how U2 snRNP undergoes remarkable movement to facilitate activation. We identify a previously unrecognized key role of PRP2 in spliceosome activation. Our study recapitulates a molecular choreography of the human spliceosome during its catalytic activation. | |||||||||
履歴 |
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構造の表示
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 398.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 75.3 KB 75.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 85.2 KB | ||
Filedesc metadata | ![]() | 22.9 KB | ||
その他 | ![]() ![]() | 392 MB 392 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8i0wMC ![]() 8i0pC ![]() 8i0rC ![]() 8i0sC ![]() 8i0tC ![]() 8i0uC ![]() 8i0vC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.077 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_35113_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_35113_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
+全体 : The human Bact-III complex
+超分子 #1: The human Bact-III complex
+分子 #1: Pre-mRNA-processing-splicing factor 8
+分子 #3: 116 kDa U5 small nuclear ribonucleoprotein component
+分子 #4: U5 small nuclear ribonucleoprotein 200 kDa helicase
+分子 #5: U5 small nuclear ribonucleoprotein 40 kDa protein
+分子 #10: Pre-mRNA-splicing factor SYF1
+分子 #11: Crooked neck-like protein 1
+分子 #12: Pre-mRNA-splicing factor SPF27
+分子 #13: Cell division cycle 5-like protein
+分子 #14: Pre-mRNA-splicing factor SYF2
+分子 #15: Protein BUD31 homolog
+分子 #16: Pre-mRNA-splicing factor RBM22
+分子 #17: Spliceosome-associated protein CWC15 homolog
+分子 #18: SNW domain-containing protein 1
+分子 #19: Peptidyl-prolyl cis-trans isomerase-like 1
+分子 #20: Pleiotropic regulator 1
+分子 #21: RNA helicase aquarius
+分子 #22: Serine/arginine repetitive matrix protein 2
+分子 #23: Pre-mRNA-splicing factor CWC22 homolog
+分子 #24: Pre-mRNA-processing factor 17
+分子 #25: Pre-mRNA-splicing factor CWC25 homolog
+分子 #26: Coiled-coil domain-containing protein 94
+分子 #27: Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16
+分子 #28: Pre-mRNA-processing factor 19
+分子 #29: Eukaryotic initiation factor 4A-III
+分子 #30: Protein mago nashi homolog
+分子 #31: RNA-binding protein 8A
+分子 #32: Protein CASC3
+分子 #33: Small nuclear ribonucleoprotein Sm D3
+分子 #34: Small nuclear ribonucleoprotein-associated proteins B and B'
+分子 #35: Small nuclear ribonucleoprotein Sm D1
+分子 #36: Small nuclear ribonucleoprotein Sm D2
+分子 #37: Small nuclear ribonucleoprotein F
+分子 #38: Small nuclear ribonucleoprotein E
+分子 #39: Small nuclear ribonucleoprotein G
+分子 #40: U2 small nuclear ribonucleoprotein A'
+分子 #41: U2 small nuclear ribonucleoprotein B''
+分子 #42: Peptidyl-prolyl cis-trans isomerase E
+分子 #43: Pre-mRNA-splicing factor ISY1 homolog
+分子 #44: Peptidylprolyl isomerase domain and WD repeat-containing protein 1
+分子 #45: Corepressor interacting with RBPJ 1
+分子 #46: WD repeat-containing protein 70
+分子 #47: Protein FRG1
+分子 #48: UNK
+分子 #2: U5 snRNA
+分子 #6: U6 snRNA
+分子 #7: pre-mRNA
+分子 #8: pre-mRNA
+分子 #9: U2 snRNA
+分子 #49: INOSITOL HEXAKISPHOSPHATE
+分子 #50: GUANOSINE-5'-TRIPHOSPHATE
+分子 #51: MAGNESIUM ION
+分子 #52: ZINC ION
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.9 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 検出モード: SUPER-RESOLUTION / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm 最小 デフォーカス(公称値): 1.4000000000000001 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: INSILICO MODEL |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 18223 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |