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Yorodumi- PDB-8ost: Structure of human terminal uridylyltransferase 4 (TUT4, ZCCHC11)... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 8ost | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | Structure of human terminal uridylyltransferase 4 (TUT4, ZCCHC11) in complex with pre-let7g miRNA and Lin28A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Keywords | CELL CYCLE / Polymerase / uridylation / RNA maturation and turnover control / RNA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationnegative regulation of glial cell differentiation / positive regulation of cell proliferation involved in kidney development / negative regulation of pre-miRNA processing / polyuridylation-dependent mRNA catabolic process / transposable element silencing by mRNA destabilization / miRNA catabolic process / protein-RNA adaptor activity / RNA uridylyltransferase / RNA 3'-end processing / pre-miRNA binding ...negative regulation of glial cell differentiation / positive regulation of cell proliferation involved in kidney development / negative regulation of pre-miRNA processing / polyuridylation-dependent mRNA catabolic process / transposable element silencing by mRNA destabilization / miRNA catabolic process / protein-RNA adaptor activity / RNA uridylyltransferase / RNA 3'-end processing / pre-miRNA binding / RNA uridylyltransferase activity / Transcriptional regulation of pluripotent stem cells / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / miRNA metabolic process / Deadenylation of mRNA / pre-miRNA processing / positive regulation of cytoplasmic translation / sequence-specific mRNA binding / oocyte maturation / miRNA binding / stem cell population maintenance / Zygotic genome activation (ZGA) / germ cell development / positive regulation of TOR signaling / rough endoplasmic reticulum / translation initiation factor binding / positive regulation of neuron differentiation / stem cell differentiation / cellular response to glucose stimulus / P-body / cytoplasmic ribonucleoprotein granule / cytoplasmic stress granule / G-quadruplex RNA binding / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / negative regulation of translation / mRNA binding / nucleolus / extracellular space / RNA binding / extracellular exosome / zinc ion binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.69 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Gilbert, R.J. / Yi, G. / Ye, M. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | United Kingdom, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024Title: Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs. Authors: Gangshun Yi / Mingda Ye / Loic Carrique / Afaf El-Sagheer / Tom Brown / Chris J Norbury / Peijun Zhang / Robert J C Gilbert / ![]() Abstract: Tumor-suppressor let-7 pre-microRNAs (miRNAs) are regulated by terminal uridylyltransferases TUT7 and TUT4 that either promote let-7 maturation by adding a single uridine nucleotide to the pre-miRNA ...Tumor-suppressor let-7 pre-microRNAs (miRNAs) are regulated by terminal uridylyltransferases TUT7 and TUT4 that either promote let-7 maturation by adding a single uridine nucleotide to the pre-miRNA 3' end or mark them for degradation by the addition of multiple uridines. Oligo-uridylation is increased in cells by enhanced TUT7/4 expression and especially by the RNA-binding pluripotency factor LIN28A. Using cryogenic electron microscopy, we captured high-resolution structures of active forms of TUT7 alone, of TUT7 plus pre-miRNA and of both TUT7 and TUT4 bound with pre-miRNA and LIN28A. Our structures reveal that pre-miRNAs engage the enzymes in fundamentally different ways depending on the presence of LIN28A, which clamps them onto the TUTs to enable processive 3' oligo-uridylation. This study reveals the molecular basis for mono- versus oligo-uridylation by TUT7/4, as determined by the presence of LIN28A, and thus their mechanism of action in the regulation of cell fate and in cancer. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | 8ost.cif.gz | 230.6 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8ost.ent.gz | 163.8 KB | Display | PDB format |
| PDBx/mmJSON format | 8ost.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/os/8ost ftp://data.pdbj.org/pub/pdb/validation_reports/os/8ost | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 17164MC ![]() 8oefC ![]() 8oppC ![]() 8opsC ![]() 8optC 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
| #1: Protein | Mass: 185433.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TUT4, KIAA0191, ZCCHC11 / Production host: ![]() | ||||
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| #2: Protein | Mass: 22778.975 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: LIN28A, CSDD1, LIN28, ZCCHC1 / Production host: ![]() | ||||
| #3: RNA chain | Mass: 22287.232 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: GenBank: 15281257 | ||||
| #4: Chemical | | Has ligand of interest | N | 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
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| Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
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| Buffer solution | pH: 7.8 | ||||||||||||||||||||||||
| 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: 2500 nm / Nominal defocus min: 1500 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.69 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 186227 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi



Homo sapiens (human)
United Kingdom, 1items
Citation








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FIELD EMISSION GUN