+
Open data
-
Basic information
Entry | Database: PDB / ID: 6sl1 | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of the open conformation of CtTel1 | ||||||
![]() | Serine/threonine-protein kinase Tel1 | ||||||
![]() | TRANSFERASE / Kinase / alpha solenoid / PIKK / nucleus / tranferase / dimer / DNA damage signaling | ||||||
Function / homology | ![]() chromatin organization / chromosome, telomeric region / non-specific serine/threonine protein kinase / DNA repair / protein serine/threonine kinase activity / ATP binding / nucleus Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
![]() | Jansma, M. / Eustermann, S.E. / Kostrewa, D. / Lammens, K. / Hopfner, K.P. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Near-Complete Structure and Model of Tel1ATM from Chaetomium thermophilum Reveals a Robust Autoinhibited ATP State. Authors: Marijke Jansma / Christian Linke-Winnebeck / Sebastian Eustermann / Katja Lammens / Dirk Kostrewa / Kristina Stakyte / Claudia Litz / Brigitte Kessler / Karl-Peter Hopfner / ![]() Abstract: Tel1 (ATM in humans) is a large kinase that resides in the cell in an autoinhibited dimeric state and upon activation orchestrates the cellular response to DNA damage. We report the structure of an ...Tel1 (ATM in humans) is a large kinase that resides in the cell in an autoinhibited dimeric state and upon activation orchestrates the cellular response to DNA damage. We report the structure of an endogenous Tel1 dimer from Chaetomium thermophilum. Major parts are at 2.8 Å resolution, including the kinase active site with ATPγS bound, and two different N-terminal solenoid conformations are at 3.4 Å and 3.6 Å, providing a side-chain model for 90% of the Tel1 polypeptide. We show that the N-terminal solenoid has DNA binding activity, but that its movements are not coupled to kinase activation. Although ATPγS and catalytic residues are poised for catalysis, the kinase resides in an autoinhibited state. The PIKK regulatory domain acts as a pseudo-substrate, blocking direct access to the site of catalysis. The structure allows mapping of human cancer mutations and defines mechanisms of autoinhibition at near-atomic resolution. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 470.8 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 385.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 815.3 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 868.2 KB | Display | |
Data in XML | ![]() | 80.9 KB | Display | |
Data in CIF | ![]() | 123 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 10234MC ![]() 6skyC ![]() 6skzC ![]() 6sl0C M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 329885.000 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() Strain: DSM 1495 / CBS 144.50 / IMI 039719 References: UniProt: G0S4S9, non-specific serine/threonine protein kinase |
---|---|
#2: Chemical | ChemComp-AGS / |
#3: Chemical | ChemComp-MG / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: CtTel1 / Type: COMPLEX / Entity ID: #1 / Source: NATURAL | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 0.64 MDa / Experimental value: YES | ||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||
Buffer solution | pH: 7.5 Details: 1 mM MgCl2 and 0.1 mM ATPgS (final concentrations) added before plunging | ||||||||||||
Buffer component |
| ||||||||||||
Specimen | Conc.: 0.15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 288.15 K Details: TWEEN-20 was added to a final concentration of 0.05% immediately before vitrification. Sample was preincubated 45 seconds before plunging into liquid ethane. |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 8 sec. / Electron dose: 55.5 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 13786 |
Image scans | Movie frames/image: 40 |
-
Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | |||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| |||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||
Particle selection | Num. of particles selected: 863937 | |||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 111910 / Symmetry type: POINT | |||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | |||||||||||||||||||||||||
Displacement parameters | Biso mean: 50.2 Å2 | |||||||||||||||||||||||||
Refine LS restraints |
|