| Protein Modification |
The complexities of the 3D structure of proteins are not the only difficulty in characterizing proteins. Many proteins contain additional chemicals that modify their structure. The final structure of a protein may include any number of modifications that occur during and after the synthesis of the protein on the ribosome. These post-translational modifications change the size and the structure of the final protein. Some modifications occur after a protein is made; others occur during translation of the protein, and are required for proper folding of the protein. One possible modification is enzymatic cleavage of the original polypeptide by proteases to produce a smaller product. Other modifications include the addition of sugar molecules to certain amino acids in the protein (glycosylation), or the addition of a phosphate group (phosphorylation) or a sulfate group (sulfation).
Many proteins are modified by proteases that remove short peptides from either end of the protein. The shortened polypeptides then fold into an active protein. One of the most common of these cleavages is the removal of specific signal peptides. These peptides target proteins for transport to a particular cellular organelle in a process known as protein sorting. An example of this is the hormone insulin, which is made as preproinsulin. After removal of the 24-amino-acid signal peptide from preproinsulin to form proinsulin, the latter polypeptide is further processed in the endoplasmic reticulum. This produces the final hormone, insulin, which is released from the cell.
Glycosylation - the addition of specific short-chain sugars to asparagine, serine, or threonine - is very common in membrane proteins that form structural components of the cell surface. These proteins, called glycoproteins, are important in many cell processes, including binding by receptors and eliciting an immune response. Glycoproteins are often specific cell markers. For example, ABO blood types result from the presence or absence of specific glycoproteins (A-type, B-type, both, or neither) on the surface of red blood cells. Human immunoglobulin G (IgG) is also a glycoprotein in which the sugar appears to very important for the normal function of the protein in the immune response. Scientists have discovered that abnormal sugars in IgG strongly correlate with the autoimmune disease called rheumatoid arthritis, characterized by chronic joint inflammation, and the presence of antibodies directed against IgG and other host proteins.
Reversible phosphorylation of threonine, serine, or tyrosine residues by enzymes called kinases (which add a phosphate) and phosphatases (which remove the phosphate) play an important role in the regulation of many cell processes, such as growth and cell cycle control. (See the Cell Biology and Cancer unit.) Phosphorylation may occur sequentially from one protein to another, resulting in a series of activations called a "phosphorylation cascade."