7K17
Re-refined crystal structure of DNA-dependent protein kinase catalytic subunit complexed with Ku80 C-terminal helix
Summary for 7K17
| Entry DOI | 10.2210/pdb7k17/pdb |
| Related | 7K0Y |
| Descriptor | DNA-dependent protein kinase catalytic subunit, X-ray repair cross-complementing protein 5 (2 entities in total) |
| Functional Keywords | nhej, v(d)j recombination, dna repair, dna binding protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 947941.00 |
| Authors | Chen, X.,Gellert, M.,Yang, W. (deposition date: 2020-09-07, release date: 2021-01-06, Last modification date: 2023-10-18) |
| Primary citation | Chen, X.,Xu, X.,Chen, Y.,Cheung, J.C.,Wang, H.,Jiang, J.,de Val, N.,Fox, T.,Gellert, M.,Yang, W. Structure of an activated DNA-PK and its implications for NHEJ. Mol.Cell, 81:801-810.e3, 2021 Cited by PubMed Abstract: DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-PK, all existing structures represent inactive states with resolution limited to 4.3 Å at best. Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms at resolutions of 3.7 Å overall and 3.2 Å for FATKINs. These structures reveal the sequential transition of DNA-PK from inactive to activated forms. Most notably, activation of the kinase involves previously unknown stretching and twisting within individual solenoid segments and loosens DNA-end binding. This unprecedented structural plasticity of helical repeats may be a general regulatory mechanism of HEAT-repeat proteins. PubMed: 33385326DOI: 10.1016/j.molcel.2020.12.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.3 Å) |
Structure validation
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