文献类型：期刊文献

英文题名：Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism

作者：You, Di[1];Yin, Bin-Cheng[1];Li, Zhi-Hai[1];Zhou, Ying[1];Yu, Wen-Bang[1];Zuo, Peng[1];Ye, Bang-Ce[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Lab Biosyst & Microanal, Shanghai 200237, Peoples R China;[2]Shihezi Univ, Sch Chem & Chem Engn, Xinjiang 832000, Peoples R China

年份：2016

卷号：113

期号：24

起止页码：6653

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000377948800038)】；

基金：This work was supported by China NSF Grants 21276079, 21421004, and 21335003; Chinese Ministry of Education Grant SRFDP 20120074110009; and 863 Program Grant 2014AA02150.

语种：英文

外文关键词：actinomycetes; protein acetylation; glutamine synthetase; nitrogen metabolism; chaperone

摘要：In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-beta) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR-DNA binding. It was observed that this regulatory function of acetylated GSI-beta enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and post-translational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes.