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- PDB-7b92: Structure of a minimal SF3B core in complex with sudemycin D6 (fo... -
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Basic information
Entry | Database: PDB / ID: 7b92 | |||||||||
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Title | Structure of a minimal SF3B core in complex with sudemycin D6 (form II) | |||||||||
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![]() | SPLICING / SF3B / pre-mRNA splicing / splicing modulator / sudemycin D6 | |||||||||
Function / homology | ![]() U11/U12 snRNP / B-WICH complex / splicing factor binding / U12-type spliceosomal complex / RNA splicing, via transesterification reactions / U2-type precatalytic spliceosome / U2-type spliceosomal complex / U2-type prespliceosome assembly / U2 snRNP / SAGA complex ...U11/U12 snRNP / B-WICH complex / splicing factor binding / U12-type spliceosomal complex / RNA splicing, via transesterification reactions / U2-type precatalytic spliceosome / U2-type spliceosomal complex / U2-type prespliceosome assembly / U2 snRNP / SAGA complex / positive regulation of transcription by RNA polymerase III / U2-type prespliceosome / precatalytic spliceosome / positive regulation of transcription by RNA polymerase I / spliceosomal complex assembly / mRNA Splicing - Minor Pathway / regulation of RNA splicing / U2 snRNA binding / regulation of DNA repair / catalytic step 2 spliceosome / mRNA Splicing - Major Pathway / RNA splicing / stem cell differentiation / spliceosomal complex / negative regulation of protein catabolic process / B-WICH complex positively regulates rRNA expression / nuclear matrix / mRNA splicing, via spliceosome / nuclear speck / chromatin remodeling / mRNA binding / protein-containing complex binding / nucleolus / positive regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / DNA binding / RNA binding / zinc ion binding / nucleoplasm / nucleus Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Cretu, C. / Pena, V. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors. Authors: Constantin Cretu / Patricia Gee / Xiang Liu / Anant Agrawal / Tuong-Vi Nguyen / Arun K Ghosh / Andrew Cook / Melissa Jurica / Nicholas A Larsen / Vladimir Pena / ![]() ![]() ![]() Abstract: Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing ...Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 471.9 KB | Display | ![]() |
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PDB format | ![]() | 302.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7b0iC ![]() 7b91C ![]() 7b9cC ![]() 7omfC ![]() 7onbC ![]() 7opiC ![]() 5ifeS ![]() 6en4S S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
-Splicing factor 3B subunit ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 100722.109 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 10149.369 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Protein | Mass: 96615.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein , 1 types, 1 molecules D
#4: Protein | Mass: 11670.525 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Non-polymers , 3 types, 5 molecules ![](data/chem/img/ZN.gif)
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#5: Chemical | #6: Chemical | ChemComp-T2W / [(~{ | #7: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.75 Å3/Da / Density % sol: 55.23 % / Description: Dome-shaped crystals |
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Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, hanging drop Details: 0.1 M HEPES pH=7.42, 0.2 M Magnesium chloride, 27.75% (v/v) PEG-400 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 22, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3→49.06 Å / Num. obs: 49623 / % possible obs: 100 % / Redundancy: 20.8 % / Biso Wilson estimate: 106.3 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.181 / Rpim(I) all: 0.041 / Rrim(I) all: 0.185 / Net I/σ(I): 14.7 |
Reflection shell | Resolution: 3→3.1 Å / Redundancy: 21.3 % / Rmerge(I) obs: 4.108 / Mean I/σ(I) obs: 0.8 / Num. unique obs: 4468 / CC1/2: 0.367 / Rpim(I) all: 0.907 / Rrim(I) all: 4.208 / % possible all: 100 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 5IFE, 6EN4 Resolution: 3→46.52 Å / SU ML: 0.6037 / Cross valid method: FREE R-VALUE / σ(F): 0.31 / Phase error: 31.3844 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 102.24 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3→46.52 Å
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Refine LS restraints |
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LS refinement shell |
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