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:
- 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 Name: Molecular Cell Journal Volume: 57 Journal Issue: 4; Journal ID: ISSN 1097-2765
- Publisher:
- Elsevier
- 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. https://doi.org/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. Sun .
"Molecular Mechanism and Evolution of Guanylate Kinase Regulation by (p)ppGpp". United States. https://doi.org/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 = {Sun Feb 01 00:00:00 EST 2015},
month = {Sun Feb 01 00:00:00 EST 2015}
}
https://doi.org/10.1016/j.molcel.2014.12.037
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