Four Primary Levels

Protein Structure on a Tertiary Level

The third of four levels of protein structure is the tertiary level. The primary level are strands of the 20 amino acids, the secondary level are alpha helix and beta pleats, the tertiary level are a combination of helix, pleats, and bends, and the quaternary level involves multiple polypeptide bonds. The tertiary level is a three dimensional level that allows the protein to be fluid and move and make up the R group in the protein structure. There are four different bonds and interactions which may be polar, nonpolar, or charged. The structure is important as it determines what that protein will do in the cell whether it be an enzyme or transporter. (Particle Sciences, 2009) . The first interaction
is a hydrophobic interaction which involves nonpolar amino acids. It is the weakest type of bond as it is incapable of hydrogen bonding or polar interactions. It resists an aqueous environment; however, this type of bond can pull proteins tightly together. The second type of bond is a hydrogen bond which involves polar amino acids. This type of bond involves a bridge between a nitrogen atom and an oxygen atom with hydrogen in between. This type of bond is stronger than a hydrophobic interaction, but is still weaker than a polypeptide chain that is present in the primary level. The third type of bond is an ionic bond that occurs between charged amino acids. This is a case where opposites attract. A negatively charged amino acid is attracted to a positively amino acid. They are yet stronger than hydrogen bonds, but still weaker than polypeptide chains. The fourth type of bond is a disulfide bond. It is a covalent bond which means that two atoms will share electrons. The cysteine amino acid is the only amino acid that can form a covalent bond by sharing a sulfide, thus creating a disulfide bond. (Particle Sciences, 2009).

F.

What is BSE?

Bovine Spongiform Encephalopathy or BSE is developed when cattle are fed prion infected meat.
It is currently thought that a normal prion protein mutates into a pathogenic form that damages the central nervous system of cattle causing the cow to act “Mad”, thus the nickname, Mad Cow Disease. It was first identified in 1986 with possible cases in the 1970’s when Scrapie infected sheep were fed to cattle in the form of meat and bone meal. Scrapie was the first transmissible spongiform encephalopathy. The feed evolved to bovine meat and bone meal and was fed to young calves. The largest outbreak in the United Kingdom took place in 1995 with 14,562 cases. In 2010, there were 11 reported cases. (Beef Checkoff,
2016)

How is a prion formed?

A prion is a pathogen that lacks nucleic acid. Though they cannot reproduce and are not susceptible to procedures that break down the nucleic acid, they can replicate by stimulating normal cellular prion protein to refold from normal prion protein to abnormal prion protein. They replicate in neural tissue causing degeneration and death. The actual process of how normal prions convert to abnormal prions remains unknown. (Beef Checkoff, 2016)

What is the connection between misfolding and aggregation?

A normal protein or PrPc has a nucleus and replicated through a folding pathway by which genetic tissue is formed. When the normal folding process is interrupted or misfolding occurs, these proteins conform to develop a prion or PrPSC that aggregates which in turn leads to degenerative disease and cell death. The connection is that the prion misfolds, and aggregates. It’s unclear still how it misfolds to begin with, but once it occurs, it attracts normal prions by “bumping” into them and continues to misfold. (T. Chaudhuri, S. Paul, 2006)

How do prions lead to the disease?

There are a number of human neurological diseases that include, but are not limited to the following: Alzheimer's disease, Parkinson's disease, Huntington's disease, and Creutzfeldt–Jakob disease, which is the human form of Bovine Spongiform Encephalopathy. These diseases are thought to be caused by the misfolding of proteins which are derived from the pathogenic prion. The prion acts as a catalyst that rapidly progresses the disease. (A. Cann, 2013)

How do chaperones normally act in the cell?

Chaperones in a cell normally “escort” the protein through the normal folding process.
How do protein chaperones contribute to BSE?

A prion acts as a chaperone and because it has been misfolded, when it bumps into normal proteins, the normal proteins then become infected and continue the misfolding process. These old and new prions aggregate on the sheath of a nerve cell causing it to degenerate which leads to BSE.

Two Ways a Country Can Decrease Transmission of BSE Cattle are more susceptible to acquiring BSE in the first 6 months of their life, but can show signs of BSE in the first 30 months. One way a country can decrease the transmission of BSE is by mandating that farmers eliminate meat and meal from their feed. The best feed for young cattle is hay, foraging, or pasture feeding. With cattle having a ruminant digestive system, this type of feed, given enough hydration, is the best for their digestive system. It also eliminates the risk of getting BSE from meat and meal feed. Another way a country can decrease the transmission of BSE is by having stricter controls on food labeling and by enforcing feed bans on meat and meal feeds that can potentially carry prion pathogens that cause BSE. (H Smith-Thomas,
2010)