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Open data
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Basic information
Entry | Database: PDB / ID: 7w59 | ||||||
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Title | The cryo-EM structure of human pre-C*-I complex | ||||||
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![]() | SPLICING / spliceosome / C* complex / RNA splicing / PRP22 / exon ligation / FAM192A | ||||||
Function / homology | ![]() 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 / negative regulation of proteasomal protein catabolic process / post-mRNA release spliceosomal complex / regulation of retinoic acid receptor signaling pathway / regulation of translation at postsynapse, modulating synaptic transmission ...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 / negative regulation of proteasomal protein catabolic process / 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 / 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 / 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 / ATP-dependent activity, acting on RNA / 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 / 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 / protein K63-linked ubiquitination / blastocyst development / protein localization to nucleus / spliceosomal tri-snRNP complex assembly / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / retinoic acid receptor signaling pathway / U5 snRNA binding Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
![]() | Zhan, X. / Lu, Y. / Shi, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Mechanism of exon ligation by human spliceosome. Authors: Xiechao Zhan / Yichen Lu / Xiaofeng Zhang / Chuangye Yan / Yigong Shi / ![]() Abstract: 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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 2.4 MB | Display | ![]() |
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PDB format | ![]() | 1.8 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 261.9 KB | Display | |
Data in CIF | ![]() | 445.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 32317MC ![]() 7w5aC ![]() 7w5bC 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 , 18 types, 19 molecules ACEJLNPRTUbiXYvwuxQ
#1: Protein | Mass: 273974.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
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#2: Protein | Mass: 109560.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#3: Protein | Mass: 39359.492 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#6: Protein | Mass: 100610.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#7: Protein | Mass: 92406.883 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#9: Protein | Mass: 17032.850 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#11: Protein | Mass: 26674.447 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#12: Protein | Mass: 61770.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#14: Protein | Mass: 57280.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#15: Protein | Mass: 300255.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() | ||||||||||||||
#21: Protein | Mass: 24642.131 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #22: Protein | | Mass: 28959.240 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #25: Protein | | Mass: 139522.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #32: Protein | | Mass: 17189.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #33: Protein | | Mass: 19925.070 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #34: Protein | | Mass: 46930.961 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #35: Protein | | Mass: 76381.992 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() #36: Protein | | Mass: 171502.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-RNA chain , 5 types, 5 molecules 4GBFH
#4: RNA chain | Mass: 14729.780 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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#5: RNA chain | Mass: 55660.688 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#18: RNA chain | Mass: 37254.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#19: RNA chain | Mass: 34404.438 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#20: RNA chain | Mass: 60186.445 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Pre-mRNA-splicing factor ... , 5 types, 5 molecules MOVIK
#8: Protein | Mass: 28780.518 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#10: Protein | Mass: 46959.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#16: Protein | Mass: 105646.578 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#23: Protein | Mass: 100148.711 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#40: 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
#13: Protein | Mass: 18257.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#24: 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
#17: Protein | Mass: 65612.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#39: 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 ahcjdkfmelgn
#26: Protein | Mass: 13940.308 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #27: Protein | Mass: 13310.653 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #28: Protein | Mass: 13551.928 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #29: Protein | Mass: 9734.171 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #30: Protein | Mass: 10817.601 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() #31: 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
#37: Protein | Mass: 28456.584 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#38: Protein | Mass: 25524.367 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 5 types, 18 molecules ![](data/chem/img/IHP.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ATP.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ATP.gif)
#41: Chemical | ChemComp-IHP / | ||||
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#42: Chemical | ChemComp-GTP / | ||||
#43: Chemical | ChemComp-MG / #44: Chemical | ChemComp-ZN / #45: Chemical | ChemComp-ATP / | |
-Details
Has ligand of interest | Y |
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-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 pre-C*-I complex / Type: COMPLEX / Entity ID: #1-#3, #6-#40 / Source: MULTIPLE SOURCES |
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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: 2500 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 192274 / Symmetry type: POINT |
Refinement | Highest resolution: 3.6 Å |