+Open data
-Basic information
Entry | Database: PDB / ID: 6l53 | ||||||
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Title | Structure of SMG1 | ||||||
Components | Serine/threonine-protein kinase SMG1 | ||||||
Keywords | TRANSFERASE / SMG1 / Cryo-EM / Nonsense-mediated mRNA decay | ||||||
Function / homology | Function and homology information diacylglycerol-dependent serine/threonine kinase activity / chromatoid body / regulation of telomere maintenance / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / telomeric DNA binding / phosphatidylinositol phosphate biosynthetic process / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / mRNA export from nucleus / peptidyl-serine phosphorylation / protein autophosphorylation ...diacylglycerol-dependent serine/threonine kinase activity / chromatoid body / regulation of telomere maintenance / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / telomeric DNA binding / phosphatidylinositol phosphate biosynthetic process / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / mRNA export from nucleus / peptidyl-serine phosphorylation / protein autophosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / protein serine kinase activity / DNA repair / protein serine/threonine kinase activity / DNA damage response / RNA binding / nucleoplasm / ATP binding / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.63 Å | ||||||
Authors | Xu, Y. / Qi, Y. | ||||||
Citation | Journal: Cell Res / Year: 2019 Title: Cryo-EM structure of SMG1-SMG8-SMG9 complex. Authors: Li Zhu / Liang Li / Yilun Qi / Zishuo Yu / Yanhui Xu / Abstract: Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of ...Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of the stress response. The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism. Here, we determined the cryo-EM structures of human SMG1 at 3.6 Å resolution and the SMG1-SMG8-SMG9 complex at 3.4 Å resolution, respectively. SMG8 has a C-terminal kinase inhibitory domain (KID), which covers the catalytic pocket and inhibits the kinase activity of SMG1. Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8-SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity. Thus, our structural and biochemical analyses provide a mechanistic understanding of SMG1-SMG8-SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6l53.cif.gz | 371.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6l53.ent.gz | 264.9 KB | Display | PDB format |
PDBx/mmJSON format | 6l53.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l5/6l53 ftp://data.pdbj.org/pub/pdb/validation_reports/l5/6l53 | HTTPS FTP |
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-Related structure data
Related structure data | 0836MC 0837C 6l54C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 410966.969 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SMG1, ATX, KIAA0421, LIP / Production host: Homo sapiens (human) References: UniProt: Q96Q15, non-specific serine/threonine protein kinase |
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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 |
-Sample preparation
Component | Name: SMG1 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: phenix.real_space_refine / Version: 1.15.2_3472 / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42688 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
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