Erratum in:- Structure (Camb). 2005 Mar;13(3):495. Maman, Joseph P [corrected to Maman, Joseph D].
Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs).
Rivera-Calzada A, Maman JD, Spagnolo L, Pearl LH, Llorca O.
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Ramiro de Maeztu 9, Campus Universidad Complutense, 28040 Madrid, Spain.
DNA-PKcs is a large PI3-kinase-related protein kinase (PIKK) that plays a central role in DNA double-strand break (DSB) repair via nonhomologous end joining. Using cryo-electron microscopy we have now generated an approximately 13 A three-dimensional map of DNA-PKcs, revealing the overall architecture and topology of the 4128 residue polypeptide chain and allowing location of domains. The highly conserved C-terminal PIKK catalytic domain forms a central structure from which FAT and FATC domains protrude. Conformational changes observed in these domains on DNA binding suggest that they transduce DNA-induced conformational changes to the catalytic core and regulate kinase activity. The N-terminal segments form long curved tubular-shaped domains based on helical repeats to create interacting surfaces required for macromolecular assembly. Comparison of DNA-PKcs with another PIKK DNA repair factor, ATM, defines a common architecture for this important protein family.
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PMID: 15698568 [PubMed - indexed for MEDLINE]