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基本情報
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タイトル | The cryo-EM structure of human C* complex | |||||||||
![]() | The cryo-EM map of human C* complex | |||||||||
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機能・相同性 | ![]() second spliceosomal transesterification activity / exon-exon junction subcomplex mago-y14 / negative regulation of selenocysteine incorporation / regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / cellular response to selenite ion / spliceosomal complex disassembly / exon-exon junction complex / selenocysteine insertion sequence binding / pre-mRNA 3'-splice site binding / granulocyte differentiation ...second spliceosomal transesterification activity / exon-exon junction subcomplex mago-y14 / negative regulation of selenocysteine incorporation / regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / cellular response to selenite ion / spliceosomal complex disassembly / exon-exon junction complex / selenocysteine insertion sequence binding / pre-mRNA 3'-splice site binding / granulocyte differentiation / regulation of translation at postsynapse, modulating synaptic transmission / negative regulation of toll-like receptor signaling pathway / post-mRNA release spliceosomal complex / regulation of retinoic acid receptor signaling pathway / renal system process / 3'-5' RNA helicase activity / U2 snRNP binding / alternative mRNA splicing, via spliceosome / intracellular mRNA localization / negative regulation of excitatory postsynaptic potential / 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 / negative regulation of interleukin-8 production / histone pre-mRNA 3'end processing complex / negative regulation of lipopolysaccharide-mediated signaling pathway / 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 / negative regulation of phosphorylation / negative regulation of interferon-beta production / 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 / ATP-dependent activity, acting on RNA / 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 / positive regulation of alpha-beta T cell differentiation / U4 snRNP / RUNX3 regulates NOTCH signaling / U2 snRNP / RNA Polymerase II Transcription Termination / NOTCH4 Intracellular Domain Regulates Transcription / exploration behavior / 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 / hematopoietic stem cell proliferation / negative regulation of type I interferon-mediated signaling pathway / negative regulation of NF-kappaB transcription factor activity / cyclosporin A binding / nuclear androgen receptor binding / regulation of alternative mRNA splicing, via spliceosome 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: 4.3 Å | |||||||||
![]() | Zhan X / Lu Y / Shi Y | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Mechanism of exon ligation by human spliceosome. 著者: Xiechao Zhan / Yichen Lu / Xiaofeng Zhang / Chuangye Yan / Yigong Shi / ![]() 要旨: Pre-mRNA splicing involves two sequential reactions: branching and exon ligation. The C complex after branching undergoes remodeling to become the C complex, which executes exon ligation. Here, we ...Pre-mRNA splicing involves two sequential reactions: branching and exon ligation. The C complex after branching undergoes remodeling to become the C complex, which executes exon ligation. Here, we report cryo-EM structures of two intermediate human spliceosomal complexes, pre-C-I and pre-C-II, both at 3.6 Å. In both structures, the 3' splice site is already docked into the active site, the ensuing 3' exon sequences are anchored on PRP8, and the step II factor FAM192A contacts the duplex between U2 snRNA and the branch site. In the transition of pre-C-I to pre-C-II, the step II factors Cactin, FAM32A, PRKRIP1, and SLU7 are recruited. Notably, the RNA helicase PRP22 is positioned quite differently in the pre-C-I, pre-C-II, and C complexes, suggesting a role in 3' exon binding and proofreading. Together with information on human C and C complexes, our studies recapitulate a molecular choreography of the C-to-C transition, revealing mechanistic insights into exon ligation. | |||||||||
履歴 |
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構造の表示
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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 | ![]() | 230.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 66.7 KB 66.7 KB | 表示 表示 | ![]() |
画像 | ![]() | 65.6 KB | ||
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 | ![]() 7w5bMC ![]() 7w59C ![]() 7w5aC 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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注釈 | The cryo-EM map of human C* complex | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.338 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
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試料の構成要素
+全体 : Human pre-C*-I complex
+超分子 #1: Human pre-C*-I 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: RNA helicase aquarius
+分子 #19: SNW domain-containing protein 1
+分子 #20: Peptidyl-prolyl cis-trans isomerase-like 1
+分子 #21: Pleiotropic regulator 1
+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: ATP-dependent RNA helicase DHX8
+分子 #26: Cactin
+分子 #27: PRKR-interacting protein 1
+分子 #28: Protein FAM32A
+分子 #29: Small nuclear ribonucleoprotein-associated proteins B and B'
+分子 #30: Peptidyl-prolyl cis-trans isomerase E
+分子 #31: Small nuclear ribonucleoprotein Sm D3
+分子 #32: Small nuclear ribonucleoprotein Sm D1
+分子 #33: Small nuclear ribonucleoprotein Sm D2
+分子 #34: Small nuclear ribonucleoprotein F
+分子 #35: Small nuclear ribonucleoprotein E
+分子 #36: Small nuclear ribonucleoprotein G
+分子 #37: Pre-mRNA-processing factor 19
+分子 #38: U2 small nuclear ribonucleoprotein A'
+分子 #39: U2 small nuclear ribonucleoprotein B''
+分子 #40: Pre-mRNA-splicing factor SLU7
+分子 #41: Protein mago nashi homolog
+分子 #42: RNA-binding protein 8A
+分子 #43: Eukaryotic initiation factor 4A-III
+分子 #44: Protein CASC3
+分子 #45: NF-kappa-B-activating protein
+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 #46: INOSITOL HEXAKISPHOSPHATE
+分子 #47: GUANOSINE-5'-TRIPHOSPHATE
+分子 #48: MAGNESIUM ION
+分子 #49: ZINC ION
+分子 #50: ADENOSINE-5'-TRIPHOSPHATE
-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 K2 SUMMIT (4k 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): 2.5 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 58374 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |