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Yorodumi- PDB-9k1w: Structure of the SF3B core, harboring the K700E mutation in SF3B1... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9k1w | ||||||
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| Title | Structure of the SF3B core, harboring the K700E mutation in SF3B1, in complex with intron-U2 snRNA | ||||||
Components |
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Keywords | SPLICING/RNA / mRNA splicing / K700E mutation / SPLICING-RNA complex | ||||||
| Function / homology | Function and homology informationU11/U12 snRNP / B-WICH complex / U12-type spliceosomal complex / RNA splicing, via transesterification reactions / splicing factor binding / U2-type precatalytic spliceosome / U2-type spliceosomal complex / U2-type prespliceosome assembly / SAGA complex / U2 snRNP ...U11/U12 snRNP / B-WICH complex / U12-type spliceosomal complex / RNA splicing, via transesterification reactions / splicing factor binding / U2-type precatalytic spliceosome / U2-type spliceosomal complex / U2-type prespliceosome assembly / SAGA complex / U2 snRNP / U2-type prespliceosome / positive regulation of transcription by RNA polymerase III / precatalytic spliceosome / spliceosomal complex assembly / positive regulation of transcription by RNA polymerase I / regulation of RNA splicing / mRNA Splicing - Minor Pathway / U2 snRNA binding / regulation of DNA repair / catalytic step 2 spliceosome / mRNA Splicing - Major Pathway / RNA splicing / stem cell differentiation / spliceosomal complex / mRNA splicing, via spliceosome / negative regulation of protein catabolic process / B-WICH complex positively regulates rRNA expression / nuclear matrix / nuclear speck / chromatin remodeling / mRNA binding / protein-containing complex binding / positive regulation of DNA-templated transcription / nucleolus / positive regulation of transcription by RNA polymerase II / DNA binding / RNA binding / zinc ion binding / nucleoplasm / nucleus Similarity search - Function | ||||||
| Biological species | Homo sapiens (human) | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
Authors | Zhang, Y. / Yin, C. / Huang, J. | ||||||
| Funding support | 1items
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Citation | Journal: Nucleic Acids Res / Year: 2025Title: A common structural mechanism for RNA recognition by the SF3B complex in mRNA splicing and export. Authors: Yuzhu Zhang / Changping Yin / Yimin Wang / Kunming Yan / Bo Zhao / Xin Hu / Youzhong Wan / Hong Cheng / Jing Huang / ![]() Abstract: The SF3B complex plays a critical role in branch point adenosine recognition during pre-mRNA splicing. Its largest subunit SF3B1 is frequently mutated in cancers, leading to aberrant alternative ...The SF3B complex plays a critical role in branch point adenosine recognition during pre-mRNA splicing. Its largest subunit SF3B1 is frequently mutated in cancers, leading to aberrant alternative splicing. Besides its function in pre-mRNA splicing, the SF3B complex also binds mature or intronless mRNAs to facilitate their nuclear export. Notably, the RNA motifs recognized by the SF3B complex exhibit no apparent sequence similarities, raising the question of how the SF3B complex recognizes diverse mRNA sequences for various cellular activities. Here we report the cryo-EM structures of the human SF3B complex associated with either intronless histone mRNAs or intron-U2 snRNA. These structures unveil that both mRNA molecules adopt a similar conformation featuring a bulged adenosine and bind the SF3B complex in a remarkably resembling manner, suggesting that SF3B recognizes the specific shape rather than the sequence of its RNA targets. Further cryo-EM and molecular dynamics analyses of the hotspot-mutant SF3B complexes bound to intron-U2 snRNA demonstrate that the SF3B1K700E and SF3B1R625H mutations similarly repel the attachment of the intronic polypyrimidine tract around the mutation sites, leading to reduced RNA-binding affinity. Altogether, our study provides structural insights into the RNA-recognition mechanism of the SF3B complex and suggests that the cancer-associated SF3B1 mutations could potentially affect multiple cellular processes including mRNA splicing and export, which advances our understanding of the pathogenic mechanisms of the SF3B1 mutations. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9k1w.cif.gz | 411.9 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9k1w.ent.gz | 319.3 KB | Display | PDB format |
| PDBx/mmJSON format | 9k1w.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9k1w_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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| Full document | 9k1w_full_validation.pdf.gz | 1.3 MB | Display | |
| Data in XML | 9k1w_validation.xml.gz | 68.3 KB | Display | |
| Data in CIF | 9k1w_validation.cif.gz | 103.7 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k1/9k1w ftp://data.pdbj.org/pub/pdb/validation_reports/k1/9k1w | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 61982MC ![]() 9k1oC ![]() 9k1qC ![]() 9k1rC ![]() 9k1yC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Splicing factor 3B subunit ... , 3 types, 3 molecules CAB
| #1: Protein | Mass: 101192.609 Da / Num. of mol.: 1 / Mutation: K700E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SF3B1, SAP155 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: O75533 |
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| #3: Protein | Mass: 136678.891 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SF3B3, KIAA0017, SAP130 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q15393 |
| #4: Protein | Mass: 10149.369 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SF3B5, SF3B10 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9BWJ5 |
-RNA chain , 2 types, 2 molecules GH
| #5: RNA chain | Mass: 10718.358 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human)Production host: in vitro transcription vector pT7-TP(deltai) (others) |
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| #6: RNA chain | Mass: 5705.339 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human)Production host: in vitro transcription vector pT7-TP(deltai) (others) |
-Protein / Non-polymers , 2 types, 4 molecules D

| #2: Protein | Mass: 12427.524 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PHF5A / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q7RTV0 |
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| #7: Chemical |
-Details
| Has ligand of interest | Y |
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| Has protein modification | N |
-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: SF3B core with K700E mutation in SF3B1 complexed with intron-U2 snRNA Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
| Buffer solution | pH: 7.5 |
| 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: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 800 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 62574 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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Trichoplusia ni (cabbage looper)
FIELD EMISSION GUN