Once translation is completed, the resulting protein can alter the phenotype of the cell or organism by affecting metabolism, signaling, gene expression, or cell structure. After translation, proteins are modified in multiple ways that regulate their structure and function. Collectively, these processes are called posttranslational modification (see Fig. 19.1e). Regulation at this level is essential because some proteins are downright dangerous. For example, proteases such as the digestive enzyme trypsin must be kept inactive until secreted out of the cell. If they were not, their activity would kill the cell. These types of protein are often controlled by being translated in inactive forms that are made active by modification after secretion.

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Folding and acquiring stability are key control points for some proteins (Chapter 4). While many proteins fold properly as they come off the ribosome, others require help from other proteins, called chaperones, which act as folding facilitators. Correct folding is important because improperly folded proteins may form aggregates that are destructive to cell function. Many diseases are associated with protein aggregates, including Alzheimer’s disease, Huntington’s disease, and the human counterpart of mad cow disease.

Posttranslational modification also helps regulate protein activity. Many proteins are modified by the addition of one or more sugar molecules to the side chains of some amino acids. This modification can alter the protein’s folding and stability, or target the molecule to particular cellular compartments. Reversible addition of a phosphate group to the side groups of amino acids such as serine, threonine, or tyrosine is a key regulator of protein activity (Chapter 9). Introduction of the negatively charged phosphate group alters the conformation of the protein, in some cases switching it from an inactive state to an active state and in other cases the reverse. Because the function of a protein molecule results from its shape and charge (Chapter 4), a change in protein conformation affects protein function.

Marking proteins for enzymatic destruction by the addition of chemical groups after translation is also important in controlling their activity. For example, we have seen how the destruction of successive waves of cyclin proteins helps move the cell through its division cycle (Chapter 11).