In nature, microbes face a spectacular array of stimuli that challenge their survival. Collectively, these stimuli exert a strong selective pressure for th evolution of sophisticated, rapid-response mechanisms that can efficiently maintain homeostasis through the modulation of functions of diverse biomolecules. Not surprisingly, biologists are interested in understanding how these mechanisms work, how they are regulated, and how they are integrated into the cellular regulatory circuits. The PI's laboratory studies the control of protein function by chemical modifications, with an emphasis on reversible lysine acylation (RLA). Ten years ago, the PI's group reported the first evidence of RLA in prokaryotes, a discovery that elicited a great deal of interest. In a short period of time, RLA has emerged as a posttranslational modification that rivals phosphorylation in terms of its breadth and impact on the dynamics of the complex metabolic network of the cell. In recent years, the PI's group has reported the impact of RLA on central cellular processes such as cell motility, gene expression, carbon metabolism, energy and coenzyme A homeostasis. The PI's laboratory studies the control of protein function by RLA. The long-term goal of the work supported by grant R01-GM062203 is to understand the contributions of RLA to cell function. The PI's group will continue to apply comprehensive genetic, molecular biological, biochemical, structural, and system-wide approaches to answer fundamental questions regarding the mechanism of RLA function. Work proposed herein seeks to: i) learn the molecular details of how acetyltransferases recognize their protein substrates;ii) gain insights into the mechanism of acetyltransferase function;iii) gain a better understanding of how proteins evolve to escape RLA control;and iv) define the regulatory circuit that integrates RLA into the complex metabolic network of the cell.

Public Health Relevance

Reversible lysine acetylation (RLA) is a regulatory mechanism for the control of protein function that offers unique opportunities for improving human health and biotechnology. Our understanding of how RLA works, how it is regulated and integrated into the metabolic network, is very limited. The proposed work will fill gaps of basic knowledge about the system in these areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM062203-13A1
Application #
8688501
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Gerratana, Barbara
Project Start
2001-01-01
Project End
2018-02-28
Budget Start
2014-07-01
Budget End
2015-02-28
Support Year
13
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Georgia
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602
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