Entry Database : EMDB / ID : EMD-6864 Structure visualization Downloads & linksTitle The Cryo-EM Structure of Human Catalytic Step I Spliceosome (C complex) at 4.1 angstrom resolution Map data Details SampleComplex : Human Catalytic Step I SpliceosomeProtein or peptide : x 41 typesRNA : x 4 typesLigand : x 6 types DetailsFunction / homology Function and homology informationFunction Domain/homology Component
exon-exon junction subcomplex mago-y14 / post-spliceosomal complex / negative regulation of selenocysteine incorporation / regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / cellular response to selenite ion / exon-exon junction complex / post-mRNA release spliceosomal complex / regulation of retinoic acid receptor signaling pathway / regulation of translation at postsynapse, modulating synaptic transmission / 3'-5' RNA helicase activity ... exon-exon junction subcomplex mago-y14 / post-spliceosomal complex / negative regulation of selenocysteine incorporation / regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / cellular response to selenite ion / exon-exon junction complex / post-mRNA release spliceosomal complex / regulation of retinoic acid receptor signaling pathway / regulation of translation at postsynapse, modulating synaptic transmission / 3'-5' RNA helicase activity / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / generation of catalytic spliceosome for first transesterification step / intracellular mRNA localization / negative regulation of excitatory postsynaptic potential / U7 snRNP / regulation of vitamin D receptor signaling pathway / histone pre-mRNA 3'end processing complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / cis assembly of pre-catalytic spliceosome / SLBP independent Processing of Histone Pre-mRNAs / regulation of mRNA processing / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / selenocysteine insertion sequence binding / 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 / Prp19 complex / 7-methylguanosine cap hypermethylation / positive regulation of androgen receptor activity / poly(A) binding / U1 snRNP binding / M-decay: degradation of maternal mRNAs by maternally stored factors / mRNA 3'-end processing / pICln-Sm protein complex / pre-mRNA binding / U2-type catalytic step 1 spliceosome / RNA splicing, via transesterification reactions / small nuclear ribonucleoprotein complex / embryonic cranial skeleton morphogenesis / sno(s)RNA-containing ribonucleoprotein complex / SMN-Sm protein complex / C2H2 zinc finger domain binding / regulation of mRNA splicing, via spliceosome / spliceosomal tri-snRNP complex / P granule / telomerase holoenzyme complex / U2-type spliceosomal complex / mRNA cis splicing, via spliceosome / positive regulation by host of viral transcription / U2-type precatalytic spliceosome / commitment complex / positive regulation of vitamin D receptor signaling pathway / Transport of Mature mRNA derived from an Intron-Containing Transcript / telomerase RNA binding / U2-type prespliceosome assembly / nuclear vitamin D receptor binding / U2-type catalytic step 2 spliceosome / U4 snRNP / Notch binding / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / RUNX3 regulates NOTCH signaling / U2 snRNP / positive regulation of mRNA splicing, via spliceosome / RNA Polymerase II Transcription Termination / NOTCH4 Intracellular Domain Regulates Transcription / U1 snRNP / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / ubiquitin-ubiquitin ligase activity / exploration behavior / WD40-repeat domain binding / NOTCH3 Intracellular Domain Regulates Transcription / positive regulation of neurogenesis / lipid biosynthetic process / U2-type prespliceosome / K63-linked polyubiquitin modification-dependent protein binding / cyclosporin A binding / nuclear androgen receptor binding / precatalytic spliceosome / Notch-HLH transcription pathway / positive regulation of transforming growth factor beta receptor signaling pathway / generation of catalytic spliceosome for second transesterification step / Formation of paraxial mesoderm / spliceosomal complex assembly / mRNA Splicing - Minor Pathway / SMAD binding / regulation of alternative mRNA splicing, via spliceosome / mitotic G2 DNA damage checkpoint signaling / associative learning / negative regulation of DNA damage response, signal transduction by p53 class mediator / protein K63-linked ubiquitination / blastocyst development / mRNA 3'-splice site recognition / protein localization to nucleus / spliceosomal tri-snRNP complex assembly Similarity search - Function CBF1-interacting co-repressor CIR, N-terminal domain / Pre-mRNA splicing factor / N-terminal domain of CBF1 interacting co-repressor CIR / Pre-mRNA splicing factor / N-terminal domain of CBF1 interacting co-repressor CIR / CASC3/Barentsz eIF4AIII binding / CASC3/Barentsz eIF4AIII binding / Btz domain / Saf4/Yju2 protein / Splicing factor Yju2 ... CBF1-interacting co-repressor CIR, N-terminal domain / Pre-mRNA splicing factor / N-terminal domain of CBF1 interacting co-repressor CIR / Pre-mRNA splicing factor / N-terminal domain of CBF1 interacting co-repressor CIR / CASC3/Barentsz eIF4AIII binding / CASC3/Barentsz eIF4AIII binding / Btz domain / Saf4/Yju2 protein / Splicing factor Yju2 / Saf4/Yju2 protein / Mago nashi protein / RNA-binding motif protein 8 / RBM8, RNA recognition motif / Mago nashi superfamily / Mago nashi protein / Pre-mRNA-splicing factor Isy1 / Pre-mRNA-splicing factor Isy1 superfamily / Isy1-like splicing family / : / : / Intron-binding protein aquarius, beta-barrel / Intron-binding protein aquarius insert domain / : / Pre-mRNA-splicing factor SPF27 / Breast carcinoma amplified sequence 2 (BCAS2) / CWF11 family / Intron-binding protein aquarius, N-terminal / Intron-binding protein aquarius N-terminal / Peptidyl-prolyl cis-trans isomerase E / Peptidyl-prolyl cis-trans isomerase E, RNA recognition motif / mRNA splicing factor SYF2 / SYF2 splicing factor / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, cyclophilin A-like / Helix hairpin bin domain superfamily / mRNA splicing factor Cwf21 domain / cwf21 domain / Pre-mRNA-processing factor 17 / : / STL11, N-terminal / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 2 / U2 small nuclear ribonucleoprotein B'', RNA recognition motif 1 / Pre-mRNA-splicing factor 19 / Pre-mRNA-processing factor 19 / : / Prp19/Pso4-like / DNA2/NAM7 helicase, helicase domain / DNA2/NAM7-like helicase / AAA domain / WD repeat Prp46/PLRG1-like / U-box domain / BUD31/G10-related, conserved site / : / : / G10 protein signature 1. / G10 protein signature 2. / SKI-interacting protein SKIP, SNW domain / SKI-interacting protein, SKIP / SKIP/SNW domain / Myb-like DNA-binding domain / Pre-mRNA-splicing factor Cwf15/Cwc15 / HAT (Half-A-TPR) repeat / Cwf15/Cwc15 cell cycle control protein / Pre-mRNA-splicing factor Cwc2/Slt11 / G10 protein / Pre-mRNA-splicing factor BUD31 / Pre-mRNA splicing factor component Cdc5p/Cef1, C-terminal / pre-mRNA splicing factor component / Initiation factor eIF-4 gamma, MA3 / MA3 domain / MI domain profile. / Domain in DAP-5, eIF4G, MA-3 and other proteins. / MIF4G domain / Small ribonucleoprotein associated, SmB/SmN / Spt5 C-terminal domain / Spt5 C-terminal nonapeptide repeat binding Spt4 / Small nuclear ribonucleoprotein D1 / U-box domain profile. / Middle domain of eukaryotic initiation factor 4G (eIF4G) / MIF4G-like, type 3 / Modified RING finger domain / U-box domain / U2A'/phosphoprotein 32 family A, C-terminal / Zinc finger, CCCH-type superfamily / occurring C-terminal to leucine-rich repeats / Leucine-rich repeat / : / Helicase associated domain (HA2), ratchet-like / Brr2, N-terminal helicase PWI domain / : / N-terminal helicase PWI domain / Pre-mRNA-splicing helicase BRR2 plug domain / zinc finger / Pre-mRNA-splicing factor Syf1-like / Sec63 Brl domain / Snu114, GTP-binding domain / DEAD-box helicase, OB fold / Oligonucleotide/oligosaccharide-binding (OB)-fold / Helicase-associated domain / Helicase associated domain (HA2), winged-helix Similarity search - Domain/homology Protein CASC3 / Pleiotropic regulator 1 / RNA helicase aquarius / Pre-mRNA-processing factor 17 / U5 small nuclear ribonucleoprotein 200 kDa helicase / Pre-mRNA-splicing factor SPF27 / Pre-mRNA-splicing factor SYF2 / U2 small nuclear ribonucleoprotein B'' / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein-associated proteins B and B' ... Protein CASC3 / Pleiotropic regulator 1 / RNA helicase aquarius / Pre-mRNA-processing factor 17 / U5 small nuclear ribonucleoprotein 200 kDa helicase / Pre-mRNA-splicing factor SPF27 / Pre-mRNA-splicing factor SYF2 / U2 small nuclear ribonucleoprotein B'' / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein-associated proteins B and B' / Eukaryotic initiation factor 4A-III / Protein BUD31 homolog / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein F / Small nuclear ribonucleoprotein G / Small nuclear ribonucleoprotein Sm D1 / Small nuclear ribonucleoprotein Sm D2 / Small nuclear ribonucleoprotein Sm D3 / Peptidyl-prolyl cis-trans isomerase G / SNW domain-containing protein 1 / 116 kDa U5 small nuclear ribonucleoprotein component / Pre-mRNA-processing-splicing factor 8 / Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 / Protein mago nashi homolog 2 / Peptidylprolyl isomerase domain and WD repeat-containing protein 1 / U5 small nuclear ribonucleoprotein 40 kDa protein / Cell division cycle 5-like protein / Splicing factor YJU2 / Crooked neck-like protein 1 / Pre-mRNA-splicing factor CWC22 homolog / Pre-mRNA-splicing factor SYF1 / Pre-mRNA-splicing factor RBM22 / Pre-mRNA-splicing factor CWC25 homolog / Spliceosome-associated protein CWC15 homolog / Pre-mRNA-splicing factor ISY1 homolog / Pre-mRNA-processing factor 19 / Peptidyl-prolyl cis-trans isomerase E / Serine/arginine repetitive matrix protein 2 / Peptidyl-prolyl cis-trans isomerase-like 1 / RNA-binding protein 8A Similarity search - ComponentBiological species Homo sapiens (human) / Human (human)Method single particle reconstruction / cryo EM / Resolution : 4.1 Å Details AuthorsZhan X / Yan C / Zhang X / Lei J / Shi Y Funding support China, 3 items Details Hide detailsOrganization Grant number Country Ministry of Science and Technology (China) 2014ZX09507003006 China National Natural Science Foundation of China 31321062 China National Natural Science Foundation of China 31130002 China
CitationJournal : Science / Year : 2018Title : Structure of a human catalytic step I spliceosome.Authors : Xiechao Zhan / Chuangye Yan / Xiaofeng Zhang / Jianlin Lei / Yigong Shi / Abstract : Splicing by the spliceosome involves branching and exon ligation. The branching reaction leads to the formation of the catalytic step I spliceosome (C complex). Here we report the cryo-electron ... Splicing by the spliceosome involves branching and exon ligation. The branching reaction leads to the formation of the catalytic step I spliceosome (C complex). Here we report the cryo-electron microscopy structure of the human C complex at an average resolution of 4.1 angstroms. Compared with the C complex, the human complex contains 11 additional proteins. The step I splicing factors CCDC49 and CCDC94 (Cwc25 and Yju2 in , respectively) closely interact with the DEAH-family adenosine triphosphatase/helicase Prp16 and bridge the gap between Prp16 and the active-site RNA elements. These features, together with structural comparison of the human C and C* complexes, provide mechanistic insights into ribonucleoprotein remodeling and allow the proposition of a working mechanism for the C-to-C* transition. History Deposition Dec 14, 2017 - Header (metadata) release Aug 8, 2018 - Map release Aug 8, 2018 - Update Oct 14, 2020 - Current status Oct 14, 2020 Processing site : PDBj / Status : Released
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