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Allosteric modulators of protein regulators

Many regulatory proteins do not function independently, instead they rely on an allosteric regulatory molecule to control their activity. These small molecules are often referred to as inducers or co-repressors or co-activators . These small molecules are often metabolites, such as lactose or tryptophan or small regulatory molecules, such as cAMP or GTP. Below are some examples of regulatory systems that are controlled by repression and by activation. In some instances the presence of the small molecule activates or enhances the DNA-binding activity of the protein, thereby allowing the protein to bind better and regulate (either activate or repress) transcription initiation. Alternatively, the small molecule interacts with the regulatory protein and inhibits or decreases its ability to interact with the DNA or RNA polymerase, which can lead to either activation or repression of the gene it is controlling.

Repressors vs activators: how do you tell

Expression of the gene

In general there are three states that can be used to described the expression of a gene or operon. The first is constitutive . That the level of expression observed under most conditions. This level of expression could be very high, if the promoter is strong, or expression could be very little, if the promoter is weak. Regardless of the amount of expression, we observe very little change in expression under a variety of conditions. The second state is activation or induction , that is under a specific set of conditions, the expression of a gene or operon is increased or activated. Finally, expression of a gene can be decreased under a certain set of conditions, this is called repression . Mechanistically, in the last two cases, regulatory proteins are required to change the constitutive expression pattern. Whether a regulatory protein acts in a positive way, that is as an activator or acts in a negative way, as a repressor is not necessarily obvious.

A simple test

So how does one determine if a regulatory protein functions in a positive or negative way? A simple genetic test is to ask "what happens to expression if the regulatory protein is absent?" If a regulatory protein is acting positively, then its presence is required to activate gene expression. In its absence, there is no regulatory protein, therefore no activation, and the out come is no transcription. The phenotype of a null mutation in a regulatory protein is no activation. The opposite is true for a regulatory protein acting negatively. In its absence expression should be increased, because the gene keeping expression low is no longer around.

Repression vs activation

What should become clear, is that how a regulatory protein functions: negatively or positively, may be independent as to what its effect is on gene expression. As you will see below, when E. coli is grown in the presence of lactose (and in the absence of glucose) expression of the lac operon is induced or activated. Yet, the protein regulator that is responsible for this expression phenotype is a repressor; it binds to the DNA to prevent transcription and a null mutation that removes the gene ( lacI ) increases expression of the lac operon. In other words, the mechanism by which a regulatory protein work (positively or negatively) is independent as to how the gene or operon is expressed and behaves. This apparent contradiction can be rationalized when you incorporate the role of the allosteric regulator; in this case lactose. As you will see in the examples below, the key to the regulation is two fold: the mechanism by which the regulator works and the role and nature of the allosteric regulator.

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Source:  OpenStax, Ucd bis2a intro to biology v1.2. OpenStax CNX. Sep 22, 2015 Download for free at https://legacy.cnx.org/content/col11890/1.1
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