Alterations Of Amino Acids
Post-translational control of protein function or structure can be accomplished by chemical alteration of an amino acid side chain or by modification of the ends of the protein backbone. While there are many diverse chemical modifications of amino acids, three common examples are phosphorylation, glycosylation, and ubiquitination.
Phosphorylation involves the addition of phosphate to an amino acid side chain, usually to the side chain hydroxyl (-OH) of serine, threonine, or tyrosine. This modification results from the action of a protein known as a kinase and uses ATP as the source of phosphate. The phosphate can be removed by another enzyme, a phosphatase. Phosphorylation can alter protein function and is relevant in cellular signaling pathways. Aberrant phosphorylation can lead to disruption of the cell cycle and the induction of cancer.
Glycosylation involves the addition of one or more sugar monomers to the side chains of amino acids, either during or after translation, to make a glycoprotein. Sugars are attached either to the side-chain nitrogen of the amino acid asparagine or to the hydroxyl of the amino acids serine or threonine. The structure of these carbohydrates can be complex and variable and often does not affect the function of proteins directly. However, glycosylation can affect the protein's solubility, its targeting to a particular part of the cell, its folding into a three-dimensional structure, its lifetime before it is degraded, and its interaction with other proteins.
The addition of ubiquitin (a protein composed of seventy-six amino acids) to another protein can render the target protein susceptible to degradation by the 26S proteosome, which is a large protease (a protein that cleaves other proteins). Ubiquitin is ubiquitous in the cell (hence its name) and varies little between organisms as diverse as yeast and humans. It is attached via the side chain of the amino acid lysine, and often additional ubiquitin proteins are added to the first to make a chain.