Skip to main content
Biology LibreTexts

8.12: Regulating protein activity

Proteins act through their interactions with other molecules. Catalytic proteins (enzymes) interact with substrate molecules; these interactions lower the activation energy of the reaction's rate limiting step, leading to an increase in the overall reaction rate. At the same time, cells and organisms are not static. They must regulate which proteins they produce, the final concentrations of those proteins within the cell (or organism), how active those proteins are, and where those proteins are located. It is primarily by altering proteins (which in turn influences gene expression) that cells (and organisms) adapt to changes in their environment.

A protein's activity can be regulated in a number of ways. The first and most obvious is to control the total number of protein molecules present within the system. Let us assume that once synthesized a protein is fully active. With this simplifying assumption, the total concentration of a protein, and the total protein activity in a system [Psys] is proportional to the rate of that protein’s synthesis (dSynthesis/dt) minus the rate of that protein’s degradation (dDegradation/dt), with dt indicating synthesis or degradation per unit time. The combination of these two processes, synthesis and degradation, determines the protein’s half-life. Since both a protein’s synthesis and degradation can be regulated, its half-life can be regulated.

The degradation of proteins is mediated by a special class of enzymes (proteins) known as proteases. Proteases cleave peptide bonds via hydrolysis (adding water) reactions. Proteases that cleave a polypeptide chain internally are known as endoproteases - they generate two polypeptides. Those that hydrolyze polypeptides from one end or the other, to release one or two amino acids at a time, are known as exoproteases. Proteases can also act more specifically, recognizing and removing specific parts of a protein in order to activate or inactivate it, or to control where it is found in a cell. For example, nuclear proteins become localized to the nucleus (typically) because they contain a nuclear localization sequence or they can be excluded because they contain a nuclear exclusion sequence. For these sequences to work they have to be able to interact with the transport machinery associated with the nuclear pores; but the protein may be folded so that they are hidden. Changes in a protein’s structure can reveal or hide such NLS or NES sequences, thereby altering the protein’s distribution within the cell and therefore its activity. As an example, a transcription factor located in the cytoplasm is inactive, but it becomes active when it enters the nucleus.Similarly, many proteins are originally synthesized in a longer and inactive "pro-form". When the pro-peptide is removed, cut away by an endoprotease, the processed protein becomes active. Proteolytic processing is itself often regulated (see below).

Controlling protein levels: Clearly the amount of a protein within a cell (or organism) is a function of the number of mRNAs encoding the protein, the rate that these mRNAs are recognized and translated, and the rate at which functional protein is formed, which in turn depends upon folding rates and their efficiency. It is generally the case that once translation begins, it continues at a more or less constant rate. In the bacterium E. coli, the rate of translation at 37ºC is about 15 amino acids per second. The translation of a polypeptide of 1500 amino acids therefore takes about 100 seconds. After translation, folding and, in multisubunit proteins, assembly, the protein will function (assuming that it is active) until it is degraded.

Many proteins within the cell are necessary all of the time. Such proteins are termed “constitutive” or house-keeping proteins. Protein degradation is particularly important for controlling the levels of “regulated” proteins, whose presence or concentration within the cell may lead to unwanted effects in certain situations. The regulated degradation of a protein typically begins when the protein is specifically marked for degradation. This is an active and highly regulated process, involving ATP hydrolysis and a multi-subunit complex known as the proteosome. The proteosome degrades the polypeptide into small peptides and amino acids that can be recycled. As a mechanism for regulating protein activity, however, degradation has a serious drawback, it is irreversible.


  • Michael W. Klymkowsky (University of Colorado Boulder) and Melanie M. Cooper (Michigan State University) with significant contributions by Emina Begovic & some editorial assistance of Rebecca Klymkowsky.