Direct binding targets of the stringent response alarmone (p)ppGpp.
The Escherichia coli stringent response, mediated by the alarmone ppGpp, is responsible for the reorganization of cellular transcription upon nutritional starvation and other stresses. These transcriptional changes occur mainly as a result of the direct effects of ppGpp and its partner transcription factor DksA on RNA polymerase. An often overlooked feature of the stringent response is the direct targeting of other proteins by ppGpp. Here we review the literature on proteins that are known to bind ppGpp and, based on sequence homology, X-ray crystal structures and in silico docking, we propose new potential protein binding targets for ppGpp. These proteins were found to fall into five main categories: (i) cellular GTPases, (ii) proteins involved in nucleotide metabolism, (iii) proteins involved in lipid metabolism, (iv) general metabolic proteins and (v) PLP-dependent basic aliphatic amino acid decarboxylases. Bioinformatic rationale is provided for expanding the role of ppGpp in regulating the activities of the cellular GTPases. Proteins involved in nucleotide and lipid metabolism and general metabolic proteins provide an interesting set of structurally varied stringent response targets. While the inhibition of some PLP-dependent decarboxylases by ppGpp suggests the existence of cross-talk between the acid stress and stringent response systems.
Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Usheer
U
Kanjee
Koji
K
Ogata
Walid A
WA
Houry
D001419:Bacteria / Q000235:genetics*; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D019295:Computational Biology; D015964:Gene Expression Regulation, Bacterial; D006158:Guanosine Pentaphosphate / Q000378:metabolism*; D006159:Guanosine Tetraphosphate / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D006159:Guanosine Tetraphosphate; D006158:Guanosine Pentaphosphate