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Open data
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Basic information
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Title | The cryo-EM structure of human C* complex | |||||||||
![]() | The cryo-EM map of human C* complex | |||||||||
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![]() | spliceosome / C* complex / RNA splicing / PRP22 / exon ligation / SPLICING | |||||||||
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 / granulocyte differentiation / post-mRNA release spliceosomal complex / renal system process / intracellular mRNA localization / U2 snRNP binding / negative regulation of toll-like receptor signaling pathway / 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 / negative regulation of interleukin-8 production / SLBP independent Processing of Histone Pre-mRNAs / negative regulation of lipopolysaccharide-mediated signaling pathway / 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 / negative regulation of interferon-beta production / 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 / U2-type spliceosomal complex / positive regulation of vitamin D receptor signaling pathway / telomerase RNA binding / telomerase holoenzyme complex / 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 / positive regulation of neurogenesis / positive regulation of alpha-beta T cell differentiation / RUNX3 regulates NOTCH signaling / U2-type catalytic step 2 spliceosome / 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 / negative regulation of type I interferon-mediated signaling pathway / WD40-repeat domain binding / inner cell mass cell proliferation / ubiquitin-ubiquitin ligase activity / nuclear androgen receptor binding / K63-linked polyubiquitin modification-dependent protein binding / precatalytic spliceosome / negative regulation of NF-kappaB transcription factor activity / cyclosporin A binding / lipid biosynthetic process / regulation of alternative mRNA splicing, via spliceosome / Notch-HLH transcription pathway / RNA polymerase II CTD heptapeptide repeat P3 isomerase activity Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.3 Å | |||||||||
![]() | Zhan X / Lu 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 230.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 73.8 KB 73.8 KB | Display Display | ![]() |
Images | ![]() | 65.6 KB | ||
Filedesc metadata | ![]() | 22.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 548.1 KB | Display | ![]() |
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Full document | ![]() | 547.7 KB | Display | |
Data in XML | ![]() | 7.3 KB | Display | |
Data in CIF | ![]() | 8.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7w5bMC ![]() 7w59C ![]() 7w5aC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
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Annotation | The cryo-EM map of human C* complex | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.338 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Human pre-C*-I complex
+Supramolecule #1: Human pre-C*-I complex
+Macromolecule #1: Pre-mRNA-processing-splicing factor 8
+Macromolecule #3: 116 kDa U5 small nuclear ribonucleoprotein component
+Macromolecule #4: U5 small nuclear ribonucleoprotein 200 kDa helicase
+Macromolecule #5: U5 small nuclear ribonucleoprotein 40 kDa protein
+Macromolecule #10: Pre-mRNA-splicing factor SYF1
+Macromolecule #11: Crooked neck-like protein 1
+Macromolecule #12: Pre-mRNA-splicing factor SPF27
+Macromolecule #13: Cell division cycle 5-like protein
+Macromolecule #14: Pre-mRNA-splicing factor SYF2
+Macromolecule #15: Protein BUD31 homolog
+Macromolecule #16: Pre-mRNA-splicing factor RBM22
+Macromolecule #17: Spliceosome-associated protein CWC15 homolog
+Macromolecule #18: RNA helicase aquarius
+Macromolecule #19: SNW domain-containing protein 1
+Macromolecule #20: Peptidyl-prolyl cis-trans isomerase-like 1
+Macromolecule #21: Pleiotropic regulator 1
+Macromolecule #22: Serine/arginine repetitive matrix protein 2
+Macromolecule #23: Pre-mRNA-splicing factor CWC22 homolog
+Macromolecule #24: Pre-mRNA-processing factor 17
+Macromolecule #25: ATP-dependent RNA helicase DHX8
+Macromolecule #26: Cactin
+Macromolecule #27: PRKR-interacting protein 1
+Macromolecule #28: Protein FAM32A
+Macromolecule #29: Small nuclear ribonucleoprotein-associated proteins B and B'
+Macromolecule #30: Peptidyl-prolyl cis-trans isomerase E
+Macromolecule #31: Small nuclear ribonucleoprotein Sm D3
+Macromolecule #32: Small nuclear ribonucleoprotein Sm D1
+Macromolecule #33: Small nuclear ribonucleoprotein Sm D2
+Macromolecule #34: Small nuclear ribonucleoprotein F
+Macromolecule #35: Small nuclear ribonucleoprotein E
+Macromolecule #36: Small nuclear ribonucleoprotein G
+Macromolecule #37: Pre-mRNA-processing factor 19
+Macromolecule #38: U2 small nuclear ribonucleoprotein A'
+Macromolecule #39: U2 small nuclear ribonucleoprotein B''
+Macromolecule #40: Pre-mRNA-splicing factor SLU7
+Macromolecule #41: Protein mago nashi homolog
+Macromolecule #42: RNA-binding protein 8A
+Macromolecule #43: Eukaryotic initiation factor 4A-III
+Macromolecule #44: Protein CASC3
+Macromolecule #45: NF-kappa-B-activating protein
+Macromolecule #2: U5 snRNA
+Macromolecule #6: U6 snRNA
+Macromolecule #7: Pre-mRNA
+Macromolecule #8: Pre-mRNA
+Macromolecule #9: U2 snRNA
+Macromolecule #46: INOSITOL HEXAKISPHOSPHATE
+Macromolecule #47: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #48: MAGNESIUM ION
+Macromolecule #49: ZINC ION
+Macromolecule #50: ADENOSINE-5'-TRIPHOSPHATE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.9 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |