title: Guanosine 5'-diphosphate 3'-diphosphate (ppGpp): positive effector for histidine operon transcription and general signal for amino-acid deficiency.
abstract: Maximal expression of the histidine operon of Salmonella typhimurium in a coupled in vitro transcription-translation system is strongly dependent upon addition of guanosine 5'-diphosphate 3'-diphosphate (ppGpp). This requirement for ppGpp is exerted at the level of transcription through a mechanism distinct from the his-operon-specific regulatory mechanism. In vivo derepression of the his operon is markedly defective when histidine starvation is imposed on a relA mutant--unable to rapidly increase synthesis of ppGpp--growing in amino-acid-rich medium. Increased sensitivity of relA mutants to growth inhibition by a number of amino-acid analogs suggests that ppGpp is generally important in adjusting expression of amino-acid-producing systems. Analysis of these findings leads us to propose that ppGpp is a positive effector in a system that enables the cell to balance endogenous amino-acid production with environmental conditions of amino-acid availability, and to compensate efficiently for transient changes in these conditions. We propose a unifying theory of the role of ppGpp as the general signal molecule (alarmone) in a "super-control" which senses an amino-acid deficiency and redirects the cell's economy in response.
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis* / Q000494:pharmacology; D005809:Genes, Regulator / Q000187:drug effects; D006150:Guanine Nucleotides / Q000378:metabolism / Q000494:pharmacology*; D006639:Histidine / Q000096:biosynthesis*; D009154:Mutation; D009876:Operon / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000596:Amino Acids; D006150:Guanine Nucleotides; D006639:Histidine