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Open data
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Basic information
Entry | Database: PDB / ID: 8i0w | ||||||
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Title | The cryo-EM structure of human C complex | ||||||
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![]() | SPLICING / spliceosome / RNA splicing / PRP16 / branching | ||||||
Function / homology | ![]() 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 Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
![]() | Zhan, X. / Lu, Y. / Shi, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis for the activation of human spliceosome. Authors: Xiechao Zhan / Yichen Lu / Yigong Shi / ![]() Abstract: 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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 2.8 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 35113MC ![]() 8i0pC ![]() 8i0rC ![]() 8i0sC ![]() 8i0tC ![]() 8i0uC ![]() 8i0vC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
+Protein , 20 types, 21 molecules ACJLNPRTQUYuvwxia3412
+RNA chain , 5 types, 5 molecules BFG6H
+U5 small nuclear ribonucleoprotein ... , 2 types, 2 molecules DE
+Pre-mRNA-splicing factor ... , 8 types, 8 molecules IKMOVXZz
+Peptidyl-prolyl cis-trans ... , 2 types, 2 molecules Sy
+Pre-mRNA-processing factor ... , 2 types, 5 molecules Wqrst
+Small nuclear ribonucleoprotein ... , 6 types, 12 molecules hgjbkcmdlenf
+U2 small nuclear ribonucleoprotein ... , 2 types, 2 molecules op
+Protein/peptide , 1 types, 1 molecules 5
+Non-polymers , 4 types, 14 molecules ![](data/chem/img/IHP.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
+Details
-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: The human Bact-III complex / Type: COMPLEX / Entity ID: #1-#6, #9-#29, #32, #31, #30 / 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 / Nominal defocus max: 2000 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 18223 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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