Structural Basis of O6-Alkylguanine Recognition by a Bacterial Alkyltransferase-like DNA Repair Protein

被引：23

作者：

Aramini, James M. ^{[1
]}

Tubbs, Julie L. ^{[2
,3
]}

Kanugula, Sreenivas ^{[4
]}

Rossi, Paolo ^{[1
]}

Ertekin, Asli ^{[1
]}

Maglaqui, Melissa ^{[1
]}

Hamilton, Keith ^{[1
]}

Ciccosanti, Colleen T. ^{[1
]}

Jiang, Mei ^{[1
]}

Xiao, Rong ^{[1
]}

Soong, Ta-Tsen ^{[5
]}

Rost, Burkhard ^{[5
]}

Acton, Thomas B. ^{[1
]}

Everett, John K. ^{[1
]}

Pegg, Anthony E. ^{[4
]}

Tainer, John A. ^{[2
,3
,6
]}

Montelione, Gaetano T. ^{[1
,7
]}

机构：

[1] Rutgers State Univ, Dept Mol Biol & Biochem, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

[2] Scripps Res Inst, Dept Mol Biol, NE Struct Genom Consortium, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Skaggs Inst Chem Biol, NE Struct Genom Consortium, La Jolla, CA 92037 USA

[4] Penn State Univ, Coll Med, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA

[5] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

[6] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, NE Struct Genom Consortium, Berkeley, CA 94720 USA

[7] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2010年 / 285卷 / 18期

关键词：

NUCLEOTIDE EXCISION-REPAIR; TORSION ANGLE DYNAMICS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; DAMAGE RECOGNITION; BACKBONE DYNAMICS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; SOFTWARE SUITE; BINDING; VALIDATION;

D O I：

10.1074/jbc.M109.093591

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：13736 / 13741

页数：6

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