5LUQ

Crystal Structure of Human DNA-dependent Protein Kinase Catalytic Subunit (DNA-PKcs)

Summary for 5LUQ

• Entry DOI: 10.2210/pdb5luq/pdb
• Descriptor: DNA-dependent protein kinase catalytic subunit,DNA-dependent Protein Kinase Catalytic Subunit,DNA-dependent protein kinase catalytic subunit, C-terminal fragment of KU80 (KU80ct194) (2 entities in total)
• Functional Keywords: dna-pkcs, kinase, dna repair, nhej, double strand break repair, heat repeat, transferase
• Biological source: Homo sapiens; More
• Cellular location: Nucleus : P78527
• Total number of polymer chains: 4
• Total formula weight: 972480.57

Authors

Sibanda, B.L.,Chirgadze, D.Y.,Ascher, D.B.,Blundell, T.L. (deposition date: 2016-09-09, release date: 2017-02-15, Last modification date: 2024-10-23)

Primary citation

Sibanda, B.L.,Chirgadze, D.Y.,Ascher, D.B.,Blundell, T.L.
DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair.
Science, 355:520-524, 2017

PubMed Abstract: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a central component of nonhomologous end joining (NHEJ), repairing DNA double-strand breaks that would otherwise lead to apoptosis or cancer. We have solved its structure in complex with the C-terminal peptide of Ku80 at 4.3 angstrom resolution using x-ray crystallography. We show that the 4128-amino acid structure comprises three large structural units: the N-terminal unit, the Circular Cradle, and the Head. Conformational differences between the two molecules in the asymmetric unit are correlated with changes in accessibility of the kinase active site, which are consistent with an allosteric mechanism to bring about kinase activation. The location of KU80ct in the vicinity of the breast cancer 1 (BRCA1) binding site suggests competition with BRCA1, leading to pathway selection between NHEJ and homologous recombination.

PubMed: 28154079
DOI: 10.1126/science.aak9654

Experimental method

X-RAY DIFFRACTION (4.3 Å)