This family consists of a number of eukaryotic proteins including CXXC motif containing zinc binding protein (previously known as UPF0587 protein C1orf123). The crystal structure reveals that the protein binds a Zn2+ ion in a tetrahedral coordination with four Cys residues from two CxxC motifs. CXXC motif containing zinc binding protein was initially identified as an interaction partner for the heavy metal-associated (HMA) domain of CCS (copper chaperone for superoxide dismutase). However, it was shown that only misfolded mutant forms, lacking part of the zinc-binding sites, interact with CCS [].
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is involved in DNA nonhomologous end joining (NHEJ) which is recruited by Ku70/80 heterodimer to DNA ends and required for double-strand break (DSB) repair. It folds into three well-defined large structural units, consisting of a N-terminal region, the Circular Cradle (consisting of five supersecondary α-helical structures CC1 to CC5), and the C-terminal Head (comprising FAT, FRB, kinase, and FATC). The N-terminal and CCs regions resemble HEAT repeats, and thus, they are also referred to as N-HEAT and M-HEAT ('middle'), respectively. The CCs form a curved elliptical ring that serves as a scaffold to maintain the integrity of the whole complex. This entry represents CC1 and CC2, which contain the Highly conserved region I (HCR-I) [, , , ].
This domain represents a region of the Circular Cradle segment (CC) from DNA-PKcs that covers the complete CC3 and part of CC4. This domain contains the Ku-binding site A and a the highly conserved region (HCR) II [].DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is involved in DNA nonhomologous end joining (NHEJ), which is recruited by Ku70/80 heterodimer to DNA ends and required for double-strand break (DSB) repair. DNA-PKcs phosphorylates a number of protein substrates, including the heat shock protein 90 (HSP90), the transcription factors p53, specificity protein 1 (Sp1) and MYC23, and a majority of NHEJ factors. It folds into three well-defined large structural units, consisting of a N-terminal region (arranged in four supersecondary α-helical structures, N1 to N4), the Circular Cradle (consisting of five supersecondary α-helical structures CC1 to CC5), and the C-terminal Head (comprising FAT, FRB, kinase, and FATC). The N-terminal and CCs regions resemble HEAT repeats, and thus, they are also referred to as N-HEAT and M-HEAT ('middle'), respectively. The N-terminal region likely mediates DNA binding and, together with the CCs, forms a ring through which Ku70/80 may present DNA for repair. The CCs form a curved elliptical ring that serves as a scaffold to maintain the integrity of the whole complex. It has been suggested that the binding of Ku or DNA activates the allosteric mechanism required for communication between the N terminus and the CC with the kinase in the Head [, , , ].
This entry represents the C-terminal region of the Circular Cradle segment (CC) of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), containing most of the supersecondary structure CC4 and the complete CC5. Structural studies revealed that this domain contains the Ku-binding site B and one of the caspase-3 cleavage sites [].DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is involved in DNA nonhomologous end joining (NHEJ), which is recruited by Ku70/80 heterodimer to DNA ends and required for double-strand break (DSB) repair. DNA-PKcs phosphorylates a number of protein substrates, including the heat shock protein 90 (HSP90), the transcription factors p53, specificity protein 1 (Sp1) and MYC23, and a majority of NHEJ factors. It folds into three well-defined large structural units, consisting of a N-terminal region (arranged in four supersecondary α-helical structures, N1 to N4), the Circular Cradle (consisting of five supersecondary α-helical structures CC1 to CC5), and the C-terminal Head (comprising FAT, FRB, kinase, and FATC). The N-terminal and CCs regions resemble HEAT repeats, and thus, they are also referred to as N-HEAT and M-HEAT ('middle'), respectively. The N-terminal region likely mediates DNA binding and, together with the CCs, forms a ring through which Ku70/80 may present DNA for repair. The CCs form a curved elliptical ring that serves as a scaffold to maintain the integrity of the whole complex. It has been suggested that the binding of Ku or DNA activates the allosteric mechanism required for communication between the N terminus and the CC with the kinase in the Head [, , , ].
