Structure of PolC reveals unique DNA binding and fidelity determinants

被引：69

作者：

Evans, Ronald J. ^{[1
]}

Davies, Douglas R. ^{[2
]}

Bullard, James M. ^{[1
]}

Christensen, Jeffrey ^{[2
]}

Green, Louis S. ^{[1
]}

Guiles, Joseph W. ^{[1
]}

Pata, Janice D. ^{[3
]}

Ribble, Wendy K. ^{[1
]}

Janjic, Nebojsa ^{[1
]}

Jarvis, Thale C. ^{[1
]}

机构：

[1] Replidyne Inc, Louisville, CO 80027 USA

[2] DeCODE Biostruct, Bainbridge Isl, WA 98110 USA

[3] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 52期

关键词：

DNA polymerase III; DNA replication; Gram-positive polymerase; polymerase and histidinol phosphatase (PHP); ternary complex;

D O I：

10.1073/pnas.0809989106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

PolC is the polymerase responsible for genome duplication in many Gram-positive bacteria and represents an attractive target for antibacterial development. We have determined the 2.4-angstrom resolution crystal structure of Geobacillus kaustophilus PolC in a ternary complex with DNA and dGTP. The structure reveals nascent base pair interactions that lead to highly accurate nucleotide incorporation. A unique beta-strand motif in the PolC thumb domain contacts the minor groove, allowing replication errors to be sensed up to 8 nt upstream of the active site. PolC exhibits the potential for large-scale conformational flexibility, which could encompass the catalytic residues. The structure suggests a mechanism by which the active site can communicate with the rest of the replisome to trigger proofreading after nucleotide misincorporation, leading to an integrated model for controlling the dynamic switch between replicative and repair polymerases. This ternary complex of a cellular replicative polymerase affords insights into polymerase fidelity, evolution, and structural diversity.

引用

页码：20695 / 20700

页数：6

共 29 条

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