title: Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein.
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.
authors.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
authors.forename: James M
authors.initials: JM
authors.lastname: Aramini
authors.forename: Julie L
authors.initials: JL
authors.lastname: Tubbs
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Kanugula
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Asli
authors.initials: A
authors.lastname: Ertekin
authors.forename: Melissa
authors.initials: M
authors.lastname: Maglaqui
authors.forename: Keith
authors.initials: K
authors.lastname: Hamilton
authors.forename: Colleen T
authors.initials: CT
authors.lastname: Ciccosanti
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Ta-Tsen
authors.initials: TT
authors.lastname: Soong
authors.forename: Burkhard
authors.initials: B
authors.lastname: Rost
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Acton
authors.forename: John K
authors.initials: JK
authors.lastname: Everett
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pegg
authors.forename: John A
authors.initials: JA
authors.lastname: Tainer
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020125:Mutation, Missense; D017510:Protein Folding; D014736:Vibrio parahaemolyticus / Q000201:enzymology* / Q000235:genetics
chemical_list: D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine; D019883:Alkyl and Aryl Transferases