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The trp operon

How the trp repressor controls expression gene expression. Feedback inhibition & attenuation.

Key points:

  • The trp operon, found in E. coli bacteria, is a group of genes that encode biosynthetic enzymes for the amino acid tryptophan.
  • The trp operon is expressed (turned "on") when tryptophan levels are low and repressed (turned "off") when they are high.
  • The trp operon is regulated by the trp repressor. When bound to tryptophan, the trp repressor blocks expression of the operon.
  • Tryptophan biosynthesis is also regulated by attenuation (a mechanism based on coupling of transcription and translation).

What is the trp operon?

Bacteria such as Escherichia coli (a friendly inhabitant of our gut) need amino acids to survive—because, like us, they need to build proteins. One of the amino acids they need is tryptophan.
If tryptophan is available in the environment, E. coli will take it up and use it to build proteins. However, E. coli can also make their own tryptophan using enzymes that are encoded by five genes. These five genes are located next to each other in what is called the trp operon.
If tryptophan is present in the environment, then E. coli bacteria don't need to synthesize it, so transcription of the genes in the trp operon is switched "off." When tryptophan availability is low, on the other hand, the operon is switched "on," the genes are transcribed, biosynthetic enzymes are made, and more tryptophan is produced.

Structure of the trp operon

The trp operon includes five genes that encode enzymes needed for tryptophan biosynthesis, along with a promoter (RNA polymerase binding site) and an operator (binding site for a repressor protein). The genes of the trp operon are transcribed as a single mRNA.

Turning the operon "on" and "off"

What does the operator do? This stretch of DNA is recognized by a regulatory protein known as the trp repressor. When the repressor binds to the DNA of the operator, it keeps the operon from being transcribed by physically getting in the way of RNA polymerase, the transcription enzyme.
The trp repressor does not always bind to DNA. Instead, it binds and blocks transcription only when tryptophan is present. When tryptophan is around, it attaches to the repressor molecules and changes their shape so they become active. A small molecule like trytophan, which switches a repressor into its active state, is called a corepressor.
When there is little tryptophan in the cell, on the other hand, the trp repressor is inactive (because no tryptophan is available to bind to and activate it). It does not attach to the DNA or block transcription, and this allows the trp operon to be transcribed by RNA polymerase.
In this system, the trp repressor acts as both a sensor and a switch. It senses whether tryptophan is already present at high levels, and if so, it switches the operon to the "off" position, preventing unnecessary biosynthetic enzymes from being made.

More trp operon regulation: Attenuation

Depending on the class you're taking, or on your own interests, you may also have heard about another form of trp operon regulation called attenuation.
Like regulation by the trp repressor, attenuation is a mechanism for reducing expression of the trp operon when levels of tryptophan are high. However, rather than blocking initiation of transcription, attenuation prevents completion of transcription.
When levels of tryptophan are high, attenuation causes RNA polymerase to stop prematurely when it's transcribing the trp operon. Only a short, stubby mRNA is made, one that does not encode any tryptophan biosynthesis enzymes. Attenuation works through a mechanism that depends on coupling (the translation of an mRNA that is still in the process of being transcribed).

Explore outside of Khan Academy

Do you want to learn more about the trp operon? Check out this scrollable interactive from LabXchange.
LabXchange is a free online science education platform created at Harvard’s Faculty of Arts and Sciences and supported by the Amgen Foundation.

Want to join the conversation?

  • piceratops tree style avatar for user Florence
    I don't understand the point attenuation.
    Attenuation of the operon allows the cell to stop (or not) the transcription of the operon before the genes coding for the enzyme, right?
    But, if the levels of tryptophan are high in the cell, wouldn't the translation of the Trp genes be already regulated via the repressor fixed on the operator ?

    What is the point in attenuation of the polymerase cannot fixe itself first? When is it used by the cell as a mean of regulation?
    (16 votes)
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    • female robot grace style avatar for user tyersome
      Great question!

      In general biological systems are quite error prone — in the case of the trp operon the repressor is reported to decrease expression by about 70 fold. Attenuation can add another 10 fold decrease in expression.

      Both mechanisms thus work together to give a better level of control.
      (25 votes)
  • blobby green style avatar for user 18kdao326
    what is the product of trp operon?
    (4 votes)
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    • blobby green style avatar for user digvijaysingh.yadav
      There are 5 structural components of trp operon as described above they produce different enzymes namely, trpE-anthranilate synthase component I, trpD - anthranilate synthase component II, trpC- N-(5'-phosphoribosyl)-anthranilate isomerase, trpB- tryptophan synthase β, and trpA- tryptophan synthase α. All of these enzymes have a combined role in production of tryptophan.
      (4 votes)
  • aqualine sapling style avatar for user Thach Dang Minh Uyen
    Why when the 1+2 và 3+4 hairpin is formed, the RNA Polymerase detaches? It's hard to understand this point...
    (4 votes)
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    • winston baby style avatar for user Ivana - Science trainee
      Look. Compare photos above and photo below. In the photo above region 4 is free to bind to RNA polymerase. Why is it important? because it encodes attenuator and promotes translation.

      However, when there is High TRp, mRNA folds and 3 and 4 region form loop. Loop makes it region 4 hidden and detaches from RNA polymerase.

      Just follow the photos and obserev them as long as you need. Tryto reproduce on paper (schematically).

      Ask more specific which part does not make sense.
      (3 votes)
  • blobby green style avatar for user cpink77
    What is the co-repressor in the trp operon?
    (3 votes)
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  • blobby green style avatar for user Ngo Quoc Phu
    why there are two codons trp? what happen if there is only one codon trp?
    (3 votes)
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    • winston baby style avatar for user Ivana - Science trainee
      Thank you for your help, now I think I may help you.

      So, there are 2 pairs of regulating genes (GDCF) but that is less relevant here. We are interested in regulating starting sequence operon.
      The operon is composed of 3 promoters (3 places for binding) but it has two Trp residues to bind two sensing signals.

      It binds L- Trp, and the other codon binds tRNA trp (charged or uncharged).

      The question arises about what would happen if only one is present (let's imagine mutation happened).

      They can function without each other. That is a form of double control.

      We can say that the principal promoter is the one binding L-Trp while Terminator is the one binding charged or uncharged tRNA Trp.

      If Trp binds to L-Trp, then it activates corepressor and diminishes the production of TRp. (it is logic high Tryptophan = no need for a synthesis of Tryptophan). However, the synthesis does not simply stop. There is wehere another promoter (terminator) that comes into place. Uncharged tRNA Trp binds and termination stops at the leading place. Meaning now translation.

      Now, what if the tRNA TRp terminator is missing? It means that translation will proceed but at a slower pace.

      What if the first codon is missing? It could potentially impair the Trp operon regulation severely. Because cells would not be able to sense whether Tryptophan is present in the cell or not.

      Hope this helps :D

      For reference, click on the https://rnajournal.cshlp.org/content/13/8/1141.full.pdf+html
      page 2 figure 2.
      (4 votes)
  • blobby green style avatar for user L.M
    What would be the easiest way to make large amounts of tryptophan, using a strain of E-Coli (through genetic engineering)? Could you please direct me in the right direction?
    (2 votes)
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    • leafers tree style avatar for user emilyabrash
      Hmm...I would say that you might want to use some of the components described in this article, but with modifications that would "break" the negative feedback loops that limit the amount of Trp produced.

      For instance, you would probably want to express the trp operon under a constitutive ("always-on") promoter, and you might also want to alter the sequence of gene encoding the gatekeeper enzyme (the one that is negatively regulated by feedback inhibition) to make it insensitive to tryptophan binding, i.e., by disrupting the tryptophan binding site. Finally, you would probably want to not include the leader of the trp operon when making the version under the constitutive promoter, or else the attenuation mechanism would prevent the accumulation of large amounts of Trp in the cell.

      I'm sure there are other ways to do it, but that would be my first thought (that you would basically need to reconstruct a version of the system that is no longer self-regulating). Hope that helps!
      (6 votes)
  • blobby green style avatar for user isacp1551
    why do the tryptophan levels go down?
    (3 votes)
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  • blobby green style avatar for user Areeb
    What does the tryptophan actually do when produced by the trp operon? If it is just produced to block the trp operon from producing more of the same substance, I don't see the point of tryptophan.
    (3 votes)
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  • blobby green style avatar for user deckermanmw
    If I were to stop the production of tryptophanase permanently in e. coli, what would happen to the cell due to the build-up of tryptophan? What about the lack of tryptophanase?
    (4 votes)
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  • blobby green style avatar for user 13m.srishti19
    Why is it that the co-repressor for Trp is Tryptophan but the co-repressor for Lac operon is allolactose.
    (3 votes)
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