Novel (p)ppGpp Binding and Metabolizing Proteins of Escherichia coli

0490330 - ÚOCHB 2019 RIV US eng J - Journal Article
Zhang, Y. - Zborníková, Eva - Rejman, Dominik - Gerdes, K.
Novel (p)ppGpp Binding and Metabolizing Proteins of Escherichia coli.
mBio. Roč. 9, č. 2 (2018), č. článku e02188-17. ISSN 2161-2129. E-ISSN 2150-7511
R&D Projects: GA ČR GA15-11711S
Institutional support: RVO:61388963
Keywords : ppGpp * E. coli * RSH
OECD category: Biochemistry and molecular biology
Impact factor: 6.747, year: 2018
http://mbio.asm.org/content/9/2/e02188-17.full

The alarmone (p) ppGpp plays pivotal roles in basic bacterial stress responses by increasing tolerance of various nutritional limitations and chemical insults, including antibiotics. Despite intensive studies since (p) ppGpp was discovered over 4 decades ago, (p) ppGpp binding proteins have not been systematically identified in Escherichia coli. We applied DRaCALA (differential radial capillary action of ligand assay) to identify (p) ppGpp-protein interactions. We discovered 12 new (p) ppGpp targets in E. coli that, based on their physiological functions, could be classified into four major groups, involved in (i) purine nucleotide homeostasis (YgdH), (ii) ribosome biogenesis and translation (RsgA, Era, HflX, and LepA), (iii) maturation of dehydrogenases (HypB), and (iv) metabolism of (p) ppGpp (MutT, NudG, TrmE, NadR, PhoA, and UshA). We present a comprehensive and comparative biochemical and physiological characterization of these novel (p) ppGpp targets together with a comparative analysis of relevant, known (p) ppGpp binding proteins. Via this, primary targets of (p) ppGpp in E. coli are identified. The GTP salvage biosynthesis pathway and ribosome biogenesis and translation are confirmed as targets of (p) ppGpp that are highly conserved between E. coli and Firmicutes. In addition, an alternative (p) ppGpp degradative pathway, involving NudG and MutT, was uncovered. This report thus significantly expands the known cohort of (p) ppGpp targets in E. coli.
Permanent Link: http://hdl.handle.net/11104/0284964