Affiliation:
1. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
2. Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Abstract
ABSTRACT
To better understand the poor conservation of the helicase binding domain of primases (DnaGs) among the eubacteria, we determined the crystal structure of the
Helicobacter pylori
DnaG C-terminal domain (
Hp
DnaG-CTD) at 1.78 Å. The structure has a globular subdomain connected to a helical hairpin. Structural comparison has revealed that globular subdomains, despite the variation in number of helices, have broadly similar arrangements across the species, whereas helical hairpins show different orientations. Further, to study the helicase-primase interaction in
H. pylori
, a complex was modeled using the
Hp
DnaG-CTD and
Hp
DnaB-NTD (helicase) crystal structures using the
Bacillus stearothermophilus
Bst
DnaB-
Bst
DnaG-CTD (helicase-primase) complex structure as a template. By using this model, a nonconserved critical residue Phe534 on helicase binding interface of DnaG-CTD was identified. Mutation guided by molecular dynamics, biophysical, and biochemical studies validated our model. We further concluded that species-specific helicase-primase interactions are influenced by electrostatic surface potentials apart from the critical hydrophobic surface residues.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
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