T4 DNA ligase structure reveals a prototypical ATP-dependent ligase with a unique mode of sliding clamp interaction

Nucleic Acids Research
Ke ShiHideki Aihara

Abstract

DNA ligases play essential roles in DNA replication and repair. Bacteriophage T4 DNA ligase is the first ATP-dependent ligase enzyme to be discovered and is widely used in molecular biology, but its structure remained unknown. Our crystal structure of T4 DNA ligase bound to DNA shows a compact α-helical DNA-binding domain (DBD), nucleotidyl-transferase (NTase) domain, and OB-fold domain, which together fully encircle DNA. The DBD of T4 DNA ligase exhibits remarkable structural homology to the core DNA-binding helices of the larger DBDs from eukaryotic and archaeal DNA ligases, but it lacks additional structural components required for protein interactions. T4 DNA ligase instead has a flexible loop insertion within the NTase domain, which binds tightly to the T4 sliding clamp gp45 in a novel α-helical PIP-box conformation. Thus, T4 DNA ligase represents a prototype of the larger eukaryotic and archaeal DNA ligases, with a uniquely evolved mode of protein interaction that may be important for efficient DNA replication.

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Citations

Oct 26, 2018·Organic & Biomolecular Chemistry·Yi LeiRyan Hili
Nov 21, 2018·Chembiochem : a European Journal of Chemical Biology·Chun GuoRyan Hili
Nov 30, 2018·Nucleic Acids Research·Shih-Hsun Chen, Xiaochun Yu
May 5, 2020·Nucleic Acids Research·Adele Williamson, Hanna-Kirsti S Leiros
May 16, 2020·Chembiochem : a European Journal of Chemical Biology·Eszter CsibraVitor B Pinheiro
Mar 4, 2019·Extremophiles : Life Under Extreme Conditions·Kristel BergAdele Williamson
Feb 20, 2021·Nature Communications·Jing ShiYu Feng
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alberto Mills, Federico Gago
Jul 22, 2021·Nucleic Acids Research·Arivazhagan RajendranTakashi Morii

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Methods Mentioned

BETA
size-exclusion chromatography
isothermal titration calorimeter
isothermal titration calorimetry

Software Mentioned

COOT
PARROT
GraphPad Prism
XDS
PHASER
3DNA
SHELXD
CURVES +
PHENIX
ImageQuant TL

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