The Structure of Protein

Proteins are formed when amino acids join through peptide bonds, which is why they are also called polypeptides. The peptide bonds between the amino acids are formed by a process called dehydration synthesis. The conformation of a protein is dependent upon physical and chemical conditions of its surrounding environment such as pH and temperature. A protein’s sequence of amino acids (a simple organic compound containing both a carboxyl and an amino group) determines how it functions. Proteins have four levels of structure: Primary, secondary, tertiary, and quaternary. The tendency of nonpolar molecules in a polar solvent to interact with one another is called the hydrophobic effect. Proteins have hydrophobic amino acids, such as glycine, clustered together within the protein. It is the amino acids with hydrophobic side chains becoming clusters at the core of a protein as a polypeptide folds into its functional shape.

Hydrogen bonding between amino groups and carboxyl groups in a protein sheet cause certain patterns of folding to occur. These hydrogen bonds cause the amino acid chain to fold or coil. This can result in two specific shapes. An alpha helix occurs when the hydrogen bonds form in a chain causing a spiraling pattern. Beta sheets form when chains that are parallel to each other link to create a pleated shape. These folding patterns make up the secondary structure of a protein.Van der Waals interactions are defined as ever-changing “hot spots of positive/negative charge” that enable atoms to stick together, due to the constant and “unsymmetrical” motion of electrons (1). In protein structures, this means that a protein has to be in a particular shape in order to function correctly. Van der Waals forces are able to do this because “slight differences in the dipole moment of two parts of the protein chain” allow these two parts to become linked together (3). It is because of this linking that proteins are able to fold into the different structures that allow them to function in the organism they occupy. Van der Waals interactions also contribute to the strength of the hydrophobic effect, because non-polar atoms are especially favored in this type of interaction (2).

Prions are proteins found on the plasma membrane (the membrane that surrounds a cell and defines its physical boundary). In mammals, prions are found in the highest concentration in cells of the central nervous system. Infection of normal cells may occur when an aberrant prion acts as a template for the refolding of a normal prion into a new aberrant prion. It is thought that there is at least one more protein involved: the as-yet-unidentified Protein X. This protein is believed to mediate the folding from a normal into an abnormal prion. When proteins are synthesized inside of a cell there are other special proteins (known as chaperones) that help in this process. Chaperones are proteins that bind to the newly synthesized protein or protein subunit, in order to ensure that the protein is properly folded into its secondary or tertiary structure. It has been hypothesized that Protein X is a type of chaperone. More studies must be done before it can be determined whether disease is caused by the lack of normal prions, or by the presence of aberrant prions. This is only one of the questions researchers are currently trying to answer. There is currently much research being conducted on the mechanism of the transformation of normal prions into mutant prions. The goal of these studies is to design drugs that can interfere with this refolding process.

Mad Cow disease is a brain disorder in adult cattle that may be spread to humans through diseased meat. Researchers believe that the infectious agent that causes mad cow disease is an abnormal version of a protein normally found on cell surfaces, called a prion. For reasons still unknown, this protein becomes altered and destroys nervous system tissue, specifically the brain and spinal cord. The human version of mad cow disease called Creutzfeldt-Jakob disease is believed to be caused by eating beef products contaminated with central nervous system tissue, such as brain and spinal cord, from cattle infected with mad cow disease. Creutzfeldt-Jakob Disease gradually destroys brain cells, and it causes tiny holes in the brain. People with CJD will have ataxia, or difficulty controlling body movements, abnormal gait, speech, and dementia. CJD happens when a prion protein, an abnormal kind of amyloid protein, causes abnormalities in other proteins. The buildup and malformation of prions on the brain cells ultimately lead to brain damage and death.