| Post-translational modification
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Many proteins must be altered by chemical modification of amino acids before the proteins become biologically active; collectively, these alterations are known as post-translational modifications. It is within the endoplasmic reticulum and Golgi apparatus that two of the major post-translational modifications of proteins occur. In the endoplasmic reticulum, an enzyme called signal peptidase removes the signal sequence from the amino-terminus of the protein, resulting in a mature protein that is 20-30 amino acids shorter than that encoded by the mRNA. In the endoplasmic reticulum and Golgi apparatus, carbohydrate side chains are added and modified at specific sites on the protein; the specific types of the carbohydrates added are important to the eventual function of the protein. A detailed description of the types of oligosaccharide side chains added to proteins, the mechanism of their addition, and the enzymes involved in this process may be found in Chapter 25.
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| Post-translational modifications to proteins may also include amino-terminal modification, modification of individual amino acids, proteolytic processing, and formation of disulfide bridges. One of the common amino-terminal modifications of eukaryotic cells is the removal of the amino-terminal methionine residue that initiates protein synthesis; in bacterial cells, the formyl group is removed from the methionine and, in some cases, the amino acid is also removed. In addition to these modifications that can occur to the amino-terminal end of the protein, amino acids within the protein can also be altered: for example, the amino acids serine, threonine, and tyrosine may have phosphate groups attached to their side chains. This type of modification is used by the cell to communicate changes in regulatory pathways resulting from hormone action and environmental stresses. Some amino acids, such as lysine, will be modified by the addition of a methyl group; others, such as cysteine, can have isoprenyl groups or other lipids added to their side
chains, to facilitate protein binding to membranes. Cysteine residues also form specific disulfide bridges that are important to the structural integrity of the protein. Finally, many proteins are synthesized as preproproteins and proproteins that must be proteolytically cleaved for them to be active. The cleavage of a precursor to its biologically active form is usually accomplished by a specific protease, and is a regulated cellular event.
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