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Title: Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp

Abstract

The nucleotide (p)ppGpp mediates bacterial stress responses, but its targets and underlying mechanisms of action vary among bacterial species and remain incompletely understood. In this paper, we characterize the molecular interaction between (p)ppGpp and guanylate kinase (GMK), revealing the importance of this interaction in adaptation to starvation. Combining structural and kinetic analyses, we show that (p)ppGpp binds the GMK active site and competitively inhibits the enzyme. The (p)ppGpp-GMK interaction prevents the conversion of GMP to GDP, resulting in GMP accumulation upon amino acid downshift. Abolishing this interaction leads to excess (p)ppGpp and defective adaptation to amino acid starvation. A survey of GMKs from phylogenetically diverse bacteria shows that the (p)ppGpp-GMK interaction is conserved in members of Firmicutes, Actinobacteria, and Deinococcus-Thermus, but not in Proteobacteria, where (p)ppGpp regulates RNA polymerase (RNAP). Finally, we propose that GMK is an ancestral (p)ppGpp target and RNAP evolved more recently as a direct target in Proteobacteria.

Authors:
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [2]
  1. Univ. of Wisconsin, Madison, WI (United States); Baylor College of Medicine, Houston, TX (United States)
  2. Univ. of Wisconsin, Madison, WI (United States)
Publication Date:
Research Org.:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1238689
Alternate Identifier(s):
OSTI ID: 1233992; OSTI ID: 1344483
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Published Article
Journal Name:
Molecular Cell
Additional Journal Information:
Journal Volume: 57; Journal Issue: 4; Journal ID: ISSN 1097-2765
Publisher:
Elsevier - Cell Press
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Liu, Kuanqing, Myers, Angela R., Pisithkul, Tippapha, Claas, Kathy R., Satyshur, Kenneth A., Amador-Noguez, Daniel, Keck, James L., and Wang, Jue D. Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp. United States: N. p., 2015. Web. doi:10.1016/j.molcel.2014.12.037.
Liu, Kuanqing, Myers, Angela R., Pisithkul, Tippapha, Claas, Kathy R., Satyshur, Kenneth A., Amador-Noguez, Daniel, Keck, James L., & Wang, Jue D. Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp. United States. doi:10.1016/j.molcel.2014.12.037.
Liu, Kuanqing, Myers, Angela R., Pisithkul, Tippapha, Claas, Kathy R., Satyshur, Kenneth A., Amador-Noguez, Daniel, Keck, James L., and Wang, Jue D. Thu . "Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp". United States. doi:10.1016/j.molcel.2014.12.037.
@article{osti_1238689,
title = {Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp},
author = {Liu, Kuanqing and Myers, Angela R. and Pisithkul, Tippapha and Claas, Kathy R. and Satyshur, Kenneth A. and Amador-Noguez, Daniel and Keck, James L. and Wang, Jue D.},
abstractNote = {The nucleotide (p)ppGpp mediates bacterial stress responses, but its targets and underlying mechanisms of action vary among bacterial species and remain incompletely understood. In this paper, we characterize the molecular interaction between (p)ppGpp and guanylate kinase (GMK), revealing the importance of this interaction in adaptation to starvation. Combining structural and kinetic analyses, we show that (p)ppGpp binds the GMK active site and competitively inhibits the enzyme. The (p)ppGpp-GMK interaction prevents the conversion of GMP to GDP, resulting in GMP accumulation upon amino acid downshift. Abolishing this interaction leads to excess (p)ppGpp and defective adaptation to amino acid starvation. A survey of GMKs from phylogenetically diverse bacteria shows that the (p)ppGpp-GMK interaction is conserved in members of Firmicutes, Actinobacteria, and Deinococcus-Thermus, but not in Proteobacteria, where (p)ppGpp regulates RNA polymerase (RNAP). Finally, we propose that GMK is an ancestral (p)ppGpp target and RNAP evolved more recently as a direct target in Proteobacteria.},
doi = {10.1016/j.molcel.2014.12.037},
journal = {Molecular Cell},
number = 4,
volume = 57,
place = {United States},
year = {2015},
month = {2}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.molcel.2014.12.037

Citation Metrics:
Cited by: 19 works
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