Download MendeleyStructural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein.
Aramini, J.M., Tubbs, J.L., Kanugula, S., Rossi, P., Ertekin, A., Maglaqui, M., Hamilton, K., Ciccosanti, C.T., Jiang, M., Xiao, R., Soong, T.T., Rost, B., Acton, T.B., Everett, J.K., Pegg, A.E., Tainer, J.A., Montelione, G.T.(2010) J Biol Chem 285: 13736-13741
- PubMed: 20212037
- DOI: https://doi.org/10.1074/jbc.M109.093591
- Primary Citation of Related Structures:
2KIF - PubMed Abstract:
Alkyltransferase-like proteins (ATLs) are a novel class of DNA repair proteins related to O(6)-alkylguanine-DNA alkyltransferases (AGTs) that tightly bind alkylated DNA and shunt the damaged DNA into the nucleotide excision repair pathway. Here, we present the first structure of a bacterial ATL, from Vibrio parahaemolyticus (vpAtl). We demonstrate that vpAtl adopts an AGT-like fold and that the protein is capable of tightly binding to O(6)-methylguanine-containing DNA and disrupting its repair by human AGT, a hallmark of ATLs. Mutation of highly conserved residues Tyr(23) and Arg(37) demonstrate their critical roles in a conserved mechanism of ATL binding to alkylated DNA. NMR relaxation data reveal a role for conformational plasticity in the guanine-lesion recognition cavity. Our results provide further evidence for the conserved role of ATLs in this primordial mechanism of DNA repair.
Organizational Affiliation:
Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. jma@cabm.rutgers.edu
