Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein

James M. Aramini, Julie L. Tubbs, Sreenivas Kanugula, Paolo Rossi, Asli Ertekin, Melissa Maglaqui, Keith Hamilton, Colleen T. Ciccosanti, Mei Jiang, Rong Xiao, Ta Tsen Soong, Burkhard Rost, Thomas B. Acton, John K. Everett, Anthony E. Pegg, John A. Tainer, Gaetano T. Montelione

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Alkyltransferase-like proteins (ATLs) are a novel class of DNA repair proteins related to O6-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 Tyr23 and Arg37 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.

Original languageEnglish (US)
Pages (from-to)13736-13741
Number of pages6
JournalJournal of Biological Chemistry
Volume285
Issue number18
DOIs
StatePublished - Apr 30 2010

Fingerprint Dive into the research topics of 'Structural basis of O<sup>6</sup>-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein'. Together they form a unique fingerprint.

Cite this