Download MendeleyThe molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase.
Bernstein, N.K., Williams, R.S., Rakovszky, M.L., Cui, D., Green, R., Karimi-Busheri, F., Mani, R.S., Galicia, S., Koch, C.A., Cass, C.E., Durocher, D., Weinfeld, M., Glover, J.N.(2005) Mol Cell 17: 657-670
- PubMed: 15749016
- DOI: https://doi.org/10.1016/j.molcel.2005.02.012
- Primary Citation of Related Structures:
1YJ5, 1YJM - PubMed Abstract:
Mammalian polynucleotide kinase (PNK) is a key component of both the base excision repair (BER) and nonhomologous end-joining (NHEJ) DNA repair pathways. PNK acts as a 5'-kinase/3'-phosphatase to create 5'-phosphate/3'-hydroxyl termini, which are a necessary prerequisite for ligation during repair. PNK is recruited to repair complexes through interactions between its N-terminal FHA domain and phosphorylated components of either pathway. Here, we describe the crystal structure of intact mammalian PNK and a structure of the PNK FHA bound to a cognate phosphopeptide. The kinase domain has a broad substrate binding pocket, which preferentially recognizes double-stranded substrates with recessed 5' termini. In contrast, the phosphatase domain efficiently dephosphorylates single-stranded 3'-phospho termini as well as double-stranded substrates. The FHA domain is linked to the kinase/phosphatase catalytic domain by a flexible tether, and it exhibits a mode of target selection based on electrostatic complementarity between the binding surface and the phosphothreonine peptide.
Organizational Affiliation:
Department of Biochemistry, 4-74 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
