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Open data
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Basic information
Entry | Database: PDB / ID: 6s8f | ||||||
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Title | Structure of nucleotide-bound Tel1/ATM | ||||||
![]() | Serine/threonine-protein kinase TEL1,Serine/threonine-protein kinase TEL1,Serine/threonine-protein kinase TEL1,Serine/threonine-protein kinase TEL1,Serine/threonine-protein kinase TEL1 | ||||||
![]() | HYDROLASE / Kinase / DNA Damage Response / CryoEM / Phosphatidylinositol-3-kinase-like kinase | ||||||
Function / homology | ![]() DNA Damage/Telomere Stress Induced Senescence / Sensing of DNA Double Strand Breaks / Pexophagy / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / phosphatidylinositol-4-phosphate binding / telomeric DNA binding / signal transduction in response to DNA damage / negative regulation of TORC1 signaling / telomere maintenance / DNA damage checkpoint signaling ...DNA Damage/Telomere Stress Induced Senescence / Sensing of DNA Double Strand Breaks / Pexophagy / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / phosphatidylinositol-4-phosphate binding / telomeric DNA binding / signal transduction in response to DNA damage / negative regulation of TORC1 signaling / telomere maintenance / DNA damage checkpoint signaling / double-strand break repair / chromatin organization / chromosome, telomeric region / non-specific serine/threonine protein kinase / protein kinase activity / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / DNA damage response / mitochondrion / ATP binding / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||
![]() | Yates, L.A. / Williams, R.M. / Ayala, R. / Zhang, X. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM Structure of Nucleotide-Bound Tel1 Unravels the Molecular Basis of Inhibition and Structural Rationale for Disease-Associated Mutations. Authors: Luke A Yates / Rhys M Williams / Sarem Hailemariam / Rafael Ayala / Peter Burgers / Xiaodong Zhang / ![]() ![]() Abstract: Yeast Tel1 and its highly conserved human ortholog ataxia-telangiectasia mutated (ATM) are large protein kinases central to the maintenance of genome integrity. Mutations in ATM are found in ataxia- ...Yeast Tel1 and its highly conserved human ortholog ataxia-telangiectasia mutated (ATM) are large protein kinases central to the maintenance of genome integrity. Mutations in ATM are found in ataxia-telangiectasia (A-T) patients and ATM is one of the most frequently mutated genes in many cancers. Using cryoelectron microscopy, we present the structure of Tel1 in a nucleotide-bound state. Our structure reveals molecular details of key residues surrounding the nucleotide binding site and provides a structural and molecular basis for its intrinsically low basal activity. We show that the catalytic residues are in a productive conformation for catalysis, but the phosphatidylinositol 3-kinase-related kinase (PIKK) regulatory domain insert restricts peptide substrate access and the N-lobe is in an open conformation, thus explaining the requirement for Tel1 activation. Structural comparisons with other PIKKs suggest a conserved and common allosteric activation mechanism. Our work also provides a structural rationale for many mutations found in A-T and cancer. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 772.4 KB | Display | ![]() |
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PDB format | ![]() | 608.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 10120MC M: map data used to model this data 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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Components
#1: Protein | Mass: 292579.406 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: TEL1, YBL088C, YBL0706 / Production host: ![]() ![]() References: UniProt: P38110, non-specific serine/threonine protein kinase #2: Chemical | #3: Chemical | Has ligand of interest | N | |
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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 |
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Sample preparation
Component | Name: Tel1/ATM / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
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: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 88.8 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 167596 / Symmetry type: POINT |