Trp operon regulation

See also Lactose Operon Regulation, Transcription Regulation in PhageA., Galactose Operon, trp Operon Regulation... 

See also trp Operon Regulation, Factor-Independent Termination of Transcription, Eukaryotic Termination of Transcription (from Chapter 28)... 

See also cAMP receptor protein (CRP), Lac Repressor, trp Operon Regulation, Arabinose Operon... 

The Lac operon is but one example of the genetic adaptations which allow bacteria to respond to their environment. Other examples are to be found in amino acid metabolism, for example the TRP operon which regulates tryptophan metabolism. 

FIGURE 28-19 The trp operon. This operon is regulated by two mechanisms when tryptophan levels are high, (1) the repressor (upper left) binds to its operator and (2) transcription of trp mRNA is attenuated (see Fig. 28-21). The biosynthesis of tryptophan by the enzymes encoded in the trp operon is diagrammed at the bottom... 

Enzymes That Catalyze Amino Acid Biosynthesis Are Regulated at the Level of Transcription Initiation The trp Operon Is Also Regulated after the Initiation Point for Transcription Genes for Ribosomes Are Coordinately Regulated Control of rRNA and tRNA Synthesis by the rel Gene... 

The trp Operon Is Also Regulated after the Initiation Point for Transcription... 

Schematic diagram of the repressor control of trp operon expression. The trp promoter (P) and trp operator (O) regions overlap. The trp aporepressor is encoded by a distantly located trpR gene. L-Tryptophan binding converts the aporepressor to the repressor that binds at the operator locus. This complex prevents the formation of the polymerase-promoter complex and transcription of the operon that begins in the leader region (trpL). Only a fraction of the transcripts extends beyond the attenuator locus in the leader region. The regulation of this fraction is discussed in the text.

The trp operon contains a cluster of five structural genes associated with tryptophan biosynthesis. Initiation of transcription of the trp operon is regulated by a repressor protein that functions similarly to the lac repressor. The main difference is that the trp repressor action is subject to control by the small-molecule effector, tryptophan. When tryptophan binds the repressor, the repressor binds to the trp operator. Thus, the effect of the small-molecule effector here is opposite to its effect on the lac operon. When tryptophan is present, there is no need for the enzymes that synthesize tryptophan. 

The trp operon has a control locus called an attenuator about 150 bases after the transcription initiation site. The attenuator is regulated by the level of charged tryptophan tRNA, so that between 10% and 90% of the elongating RNA polymerases transcribe through this site to the end of the operon. Low levels of trp tRNA encourage transcription through the attenuator. 

The trp operon is regulated by both repression (which determines whether transcription will occur or not) and attenuation (which fine tunes transcription). Other operons for amino acid biosynthetic pathways may also be regulated by both repression and attenuation or only by attenuation. 

Fig. 1. Regulation of the trp operon (a) transcription in the absence of tryptophan (b) no transcription in the presence of tryptophan.

TrpR, which is a DNA binding repressor protein, regulates transcription initiation of the E. coli trpEDCBA operon. Under tryptophan limiting conditions, TrpR represses transcription initiation, whereas repression is relieved in the presence of excess tryptophan. Once transcription initiates the elongating transcription complex is subject to control by transcription attenuation (reviewed in References 5 and 6). The leader transcript can form three RNA secondary structures that are referred to as the pause hairpin, the antiterminator structure, and an intrinsic terminator hairpin. Because the antiterminator shares nucleotides in common with the terminator, their formation is mutually exclusive. The pause hairpin has two additional roles in this transcription attenuation mechanism it serves as an anti-antiterminator stmc-ture that prevents antiterminator formation, and it codes for a leader peptide. A model of the E. coli trp operon transcription attenuation mechanism is presented in Fig. 2a. 

Regulation of the trp operon is determined by the concentration of tryptophan when adequate tryptophan is present in the growth medium, there is no need for tryptophan biosynthesis. Transcription is turned off when a high concentration of tryptophan is present and is turned on when tryptophan is absent. The regulatory signal is the concentration of tryptophan itself and, in contrast with lactose, tryptophan is active in repression rather than induction. 

The trp operon has two levels of regulation—an on-off mechanism and a modulation system. The protein product of the trpR gene—the trp aporepressor—cannot bind to the operator in contrast with the lac repressor. However, if tryptophan is present, the aporepressor and the tryptophan molecule join together to form an active repressor complex... 

Fig. 1.15 Regulation ofthe Trp operon in coli. A) The Trp repressor requires Trp in order to bind its affiliated DNA binding element. In the absence of tryptophan, the Trp repressor can not bind to the regulatory sequence and is therefor inactive. Upon an increase in the tryptohan concentration, tryptophan binds to the Trp repressor and transforms it into a binding-proficient form. The DNA bound Trp repressor prevents the transcription ofthe structural genes, and the biosynthesis of tryptophan is halted. B) structural basis for the activation ofthe...

In addition to repression, the trp operon is regulated by transcription attenuation. This control mechanism works by altering transcription after it has begun via transcription termination or pausing. Prokaryotes have no separation... 

The phenomenon of attenuation of translation of the trp operon in bacteria is provided as an example of posttranscriptional gene regulation. This mechanism, which is used by several amino acid biosynthetic operons, relies on alternative RNA secondary structures and on the coupling of transcription and translation in prokaryotes. The regulation of iron metabolism in animals is presented to show how RNA secondary structures can by bound specifically by proteins and thereby regulate translation. 

Provide an overview of the regulation of the tryptophan (trp) operon by attenuation. 

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