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- PDB-6icz: Cryo-EM structure of a human post-catalytic spliceosome (P comple... -
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Basic information
Entry | Database: PDB / ID: 6icz | |||||||||
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Title | Cryo-EM structure of a human post-catalytic spliceosome (P complex) at 3.0 angstrom | |||||||||
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![]() | SPLICING / Human Post-catalytic Spliceosome | |||||||||
Function / homology | ![]() 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 / selenocysteine insertion sequence binding / exon-exon junction complex / pre-mRNA 3'-splice site binding / regulation of translation at postsynapse, modulating synaptic transmission / regulation of retinoic acid receptor signaling pathway ...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 / selenocysteine insertion sequence binding / exon-exon junction complex / pre-mRNA 3'-splice site binding / regulation of translation at postsynapse, modulating synaptic transmission / regulation of retinoic acid receptor signaling pathway / post-mRNA release spliceosomal complex / renal system process / intracellular mRNA localization / U2 snRNP binding / U7 snRNA binding / histone pre-mRNA DCP binding / 3'-5' RNA helicase activity / U7 snRNP / generation of catalytic spliceosome for first transesterification step / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / histone pre-mRNA 3'end processing complex / alternative mRNA splicing, via spliceosome / cis assembly of pre-catalytic spliceosome / regulation of mRNA processing / regulation of vitamin D receptor signaling pathway / negative regulation of excitatory postsynaptic potential / SLBP independent Processing of Histone Pre-mRNAs / SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs / Deadenylation of mRNA / spliceosome conformational change to release U4 (or U4atac) and U1 (or U11) / nuclear retinoic acid receptor binding / embryonic brain development / protein methylation / U12-type spliceosomal complex / oocyte development / embryonic cranial skeleton morphogenesis / poly(A) binding / 7-methylguanosine cap hypermethylation / RNA splicing, via transesterification reactions / U1 snRNP binding / mRNA 3'-end processing / M-decay: degradation of maternal mRNAs by maternally stored factors / sno(s)RNA-containing ribonucleoprotein complex / methylosome / ATP-dependent activity, acting on RNA / regulation of mRNA splicing, via spliceosome / pICln-Sm protein complex / C2H2 zinc finger domain binding / U2-type catalytic step 1 spliceosome / pre-mRNA binding / positive regulation of mRNA splicing, via spliceosome / snRNP binding / small nuclear ribonucleoprotein complex / SMN-Sm protein complex / P granule / host-mediated activation of viral transcription / spliceosomal tri-snRNP complex / U2-type precatalytic spliceosome / telomerase holoenzyme complex / U2-type spliceosomal complex / positive regulation of vitamin D receptor signaling pathway / telomerase RNA binding / commitment complex / mRNA cis splicing, via spliceosome / U2-type prespliceosome assembly / nuclear vitamin D receptor binding / Transport of Mature mRNA derived from an Intron-Containing Transcript / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / Notch binding / RUNX3 regulates NOTCH signaling / U2-type catalytic step 2 spliceosome / positive regulation of neurogenesis / NOTCH4 Intracellular Domain Regulates Transcription / U4 snRNP / U2 snRNP / RNA Polymerase II Transcription Termination / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / U1 snRNP / NOTCH3 Intracellular Domain Regulates Transcription / protein peptidyl-prolyl isomerization / U2-type prespliceosome / inner cell mass cell proliferation / WD40-repeat domain binding / ubiquitin-ubiquitin ligase activity / nuclear androgen receptor binding / K63-linked polyubiquitin modification-dependent protein binding / precatalytic spliceosome / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity / RNA polymerase II CTD heptapeptide repeat P6 isomerase activity / cyclosporin A binding / lipid biosynthetic process / regulation of alternative mRNA splicing, via spliceosome / Notch-HLH transcription pathway / Formation of paraxial mesoderm / SMAD binding / protein kinase inhibitor activity / positive regulation of transforming growth factor beta receptor signaling pathway / spliceosomal complex assembly / exploration behavior / mitotic G2 DNA damage checkpoint signaling Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | |||||||||
![]() | Zhang, X. / Zhan, X. / Yan, C. / Shi, Y. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of the human spliceosomes before and after release of the ligated exon. Authors: Xiaofeng Zhang / Xiechao Zhan / Chuangye Yan / Wenyu Zhang / Dongliang Liu / Jianlin Lei / Yigong Shi / ![]() Abstract: Pre-mRNA splicing is executed by the spliceosome, which has eight major functional states each with distinct composition. Five of these eight human spliceosomal complexes, all preceding exon ...Pre-mRNA splicing is executed by the spliceosome, which has eight major functional states each with distinct composition. Five of these eight human spliceosomal complexes, all preceding exon ligation, have been structurally characterized. In this study, we report the cryo-electron microscopy structures of the human post-catalytic spliceosome (P complex) and intron lariat spliceosome (ILS) at average resolutions of 3.0 and 2.9 Å, respectively. In the P complex, the ligated exon remains anchored to loop I of U5 small nuclear RNA, and the 3'-splice site is recognized by the junction between the 5'-splice site and the branch point sequence. The ATPase/helicase Prp22, along with the ligated exon and eight other proteins, are dissociated in the P-to-ILS transition. Intriguingly, the ILS complex exists in two distinct conformations, one with the ATPase/helicase Prp43 and one without. Comparison of these three late-stage human spliceosomes reveals mechanistic insights into exon release and spliceosome disassembly. | |||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 2.7 MB | Display | ![]() |
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PDB format | ![]() | 1.9 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.8 MB | Display | ![]() |
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Full document | ![]() | 2 MB | Display | |
Data in XML | ![]() | 310.8 KB | Display | |
Data in CIF | ![]() | 528.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9645MC ![]() 9646C ![]() 9647C ![]() 6id0C ![]() 6id1C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
-Protein , 17 types, 18 molecules vwuxACJLNPRTUXQibY
#1: Protein | Mass: 17301.799 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
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#2: Protein | Mass: 19925.070 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#3: Protein | Mass: 46930.961 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#4: Protein | Mass: 76381.992 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#5: Protein | Mass: 273974.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#7: Protein | Mass: 109560.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#12: Protein | Mass: 100610.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#13: Protein | Mass: 92406.883 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#15: Protein | Mass: 17032.850 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#17: Protein | Mass: 26674.447 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#18: Protein | Mass: 61770.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#20: Protein | Mass: 57280.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#21: Protein | Mass: 300255.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#24: Protein | Mass: 21040.176 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#28: Protein | Mass: 171502.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||
#30: Protein | Mass: 23686.004 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #38: Protein | | Mass: 139522.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-RNA chain , 4 types, 4 molecules BFGH
#6: RNA chain | Mass: 37254.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#9: RNA chain | Mass: 34404.438 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#10: RNA chain | Mass: 87382.422 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#11: RNA chain | Mass: 60186.445 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-U5 small nuclear ribonucleoprotein ... , 2 types, 2 molecules ED
#8: Protein | Mass: 39359.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#41: Protein | Mass: 244823.422 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Pre-mRNA-splicing factor ... , 6 types, 6 molecules MOVZIK
#14: Protein | Mass: 28780.518 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#16: Protein | Mass: 46959.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#22: Protein | Mass: 105646.578 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#25: Protein | Mass: 68510.844 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#26: Protein | Mass: 100148.711 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#39: Protein | Mass: 26163.420 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Peptidyl-prolyl cis-trans ... , 2 types, 2 molecules Sy
#19: Protein | Mass: 18257.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#27: Protein | Mass: 33475.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Pre-mRNA-processing factor ... , 2 types, 5 molecules Wqrst
#23: Protein | Mass: 65612.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#40: Protein | Mass: 55245.547 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: Q9UMS4, RING-type E3 ubiquitin transferase |
-Small nuclear ribonucleoprotein ... , 6 types, 12 molecules hajckdmfleng
#29: Protein | Mass: 13940.308 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #31: Protein | Mass: 13310.653 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #32: Protein | Mass: 13551.928 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #33: Protein | Mass: 9734.171 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #34: Protein | Mass: 10817.601 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #35: Protein | Mass: 8508.084 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-U2 small nuclear ribonucleoprotein ... , 2 types, 2 molecules op
#36: Protein | Mass: 28456.584 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#37: Protein | Mass: 25524.367 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 5 types, 19 molecules 








#42: Chemical | ChemComp-IHP / | ||||
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#43: Chemical | ChemComp-GTP / | ||||
#44: Chemical | ChemComp-MG / #45: Chemical | ChemComp-ZN / #46: Chemical | ChemComp-ATP / | |
-Details
Has protein modification | Y |
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Sequence details | The residue N (unknown nucleotide) between G-1 and G1 is added intentionally to fill in the ...The residue N (unknown nucleotide) between G-1 and G1 is added intentionally to fill in the cleavage by RNA splicing. |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Human Post_catalytic Spliceosome / Type: COMPLEX / Entity ID: #1-#41 / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.9 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 143320 / Symmetry type: POINT |
Refinement | Highest resolution: 3 Å |