Hydrophobic Interactions: Misfolded Proteins

Out of the many forms of infectious agents, one that seemingly defies the central dogma of biology is the prion. These types of diseases are created when an otherwise suitable protein is altered in a prion like domain, becomes misfolded, and begins contorting other specimens of the same protein to this misfolded shape resulting in what’s known as an amyloid fiber. This entire replication process does not require DNA, simply more of the non-mutated protein. Recent studies focusing on mutations identified in two heterogeneous nuclear ribonucleicprotiens, hnRNPA2B1 and hnRNPA1, have shown to produce cytoplasmic inclusions. This causes mass degradation of muscle tissues and structures throughout the human body known as multisystem

Correct folding of proteins is important for our bodies to function properly. Proteins consist of amino acids and are the building blocks of our body. Just the incorrect folding of a protein can have serious consequences for the organism. It seems that the molecular chaperones that fold proteins are dysfunctional in PD patients.

Author Beata Sikorska writes a chapter on this disease in the book Neurodegenerative Diseases, she discusses how this rare disease is caused by an abnormal piece of protein (PrP) called a prion (Sikorska, 2012). A prion is an infectious particle made of proteins and the specific protein PrP is the human gene encoding expressed mostly in the nervous system. Proteins are made up by a string of amino acids that fold and form a 3-D shape; the shape the amino acids take gives these proteins it’s function. When a protein does not fold properly it does not function or can become destructive. The human body has specific mechanisms to protect itself from many different types of infections; one of these mechanisms is the blood brain barrier. This barrier blocks harmful substances from entering the brain while allowing necessary nutrients in this includes allowing PrP proteins to enter. Marie-Clare Porter describes the process of CJD in the British Journal of Anesthesia as a prion which is also known as transmissible spongiform encephalopathies, are a group of neurodegenerative conditions that are transmissible, progressive and uniformly fatal (Porter, 2013). Once a prion enters the brain it can infect other normal proteins causing them to lose function and become destructive. As the affected brain cells continue to die they leave tiny sponge-like holes; these holes eventually lead to the signs and symptoms of CJD and are

Generally, a sponge is equated with the soaking or consumption of liquids. Nevertheless, this is not representative of this disease or its effects on the human brain. This progressive and debilitating disease maintains many unknowns, and patient outlook is equivalent to lethal injection. Creutzfeldt-Jakob’s Disease (CJD) is a rare, degenerative, invariably fatal brain disorder, derived from transmissible spongiform encephalopathy caused by prions. Prions occur in a normal state, which are harmless proteins found in the body’s cells, and also in an infectious form that causes disease. Harmless forms of prion proteins have the same sequence of amino acids, but the infectious forms of protein have a different folded shape than normal proteins.

Creutzfeldt-Jakob Disease is a rare neurodegenerative disorder that is caused by a unique infectious agent called prion. It is neither a virus or bacteria and is not even a living organism but purely a protein that infects the brain causing neuro-degradation and eventually death. CJD is the human disorder from a family of prion diseases which have also been found in animals such as sheep called Scrapie Disease, cattle known as Bovine Spongiform Encephalitis, and deer named Chronic Wasting Disease (Anderson, Salm, Allen, 2016, p.356). Researchers found that this prion disease is caused by a misfolding of a normal prion-related protein, PrPc. These normal proteins are genetically synthesized proteins normally found on surfaces of neurons. While there are still uncertainties about the functions of these normal PrPc proteins, there is some evidence that it is

Transmissible Spongiform Encephalopathies (TSEs), sometimes referred to as prion diseases, are a series of rare degenerative brain disorders portrayed by miniature holes that makes the brain the same appearance as a sponge. TSEs are caused by an unusual version of a protein called a proteinaceous infectious particle, also known as a prion. Prions can occur in a normal form, which does not cause harm to the body’s cells, and in an infectious form, which causes substantial harm to the body’s cells. Both forms of the prion are almost identical, but the harmful form has a distinctive folded shape. TSEs has the ability to occur sporadically, hereditary, or transmitted from an infected individual. Sporadic TSEs can develop with no cause. In some

14. Which of the following is not one of the functional roles of membrane proteins?

A hydrogen bond is the chemical bond in which a hydrogen atom is attracted to an electromagnetic atom (YourDictionary). Water molecules can be bonded together when attracted to one another and this creates more and more water. The positive charge of the hydrogen attract to the negative charge oxygen. This bond is similar to how dogs interact with one another. Dogs tend to sniff the behind of other dogs. The nose of a dog can be the positive charge and the negative charge be the behind. When a dog sniffs the behind of another dog, it resembles a hydrogen atom attracting to an oxygen atom. When water molecules are close together, their positive and negative areas are attracted to the oppositely charged areas of the molecule. Hydrogen bonding

As scientists, we are always trying to discover the answers to the how and why questions that comes up as science progresses. We all know that nothing is ever straight forward and sometimes we end up with more questions than answers from our obtained results but this is not always a negative. A major area of interest today is the development and progression of amyloid diseases such as Alzheimer’s’ disease, Huntington’s disease, and transmissible bovine spongiform encephalopathy. Despite extensive studies conducted on each one of these diseases, little is really known about their development and progression because little is known about the mechanism behind amyloid fibril formation – the common link found in all of these diseases. Over the

Amino acids have attributes that make them hydrophilic or hydrophobic. Amino acids that contain electrically side chains are able to connect or attract with water molecules. Amino acids that contain partial charges or polar side chains, forming hydrogen bonds, are hydrophilic or attract with water molecules. Amino acids with nonpolar side chains are hydrophobic or do not attract with water molecules.

Hypothesis: If a polar amino acid is adsorbed by a polar matrix, then the polar matrix will not move as far along the matrix as a hydrophobic amino acid. If this is so, the Rf value of a polar amino acid will be relatively small to that of a non-polar amino acid.

The primary protein structure can be likened to a human chain in which each person is assumed to be an amino acid and their hands viewed as the carboxyl and amino groups. The person on one end of the chain, who has a free left hand, is assumed to be the free carboxyl group. The person on the other end, who has a free right hand, is assumed to be the free amino group. Everyone in this chain has a left hand linked to somebody’s right hand and a right hand linked to somebody else’s left hand forming peptide bonds. The heads and legs just like the side chains and hydrogens, do not take part in the linking.

3. The structure of a protein such as hemoglobin is very similar to an enzyme. The primary structure is the amino acid sequence. The secondary structure is the bonding of primary structures with the use of hydrogen. Tertiary structure is the bonding of the previous stage by covalent bonds. The final Quarternary structure involves more than one amino acid sequence. When a protein such as hemoglobin is heated, its bonds will be broken, causing a delay on the speed in which it is able to carry oxygen.

One clear example of how mutations in the Prion like domains can affect the protein is shown in a study done by James Shorter and J. Paul Taylor, continuing the research of Hong Joo Kim et al. During the original research, mutations were found in the PrLDs of both hnRNPA1 and hnRNPA2/B1, that may have a connection to forms of multisystem proteinopathy (MSP) such as ALS. When looking into a family that was afflicted by a MSP they found a mutation within RNA binding proteins known hnRNPA2/B1. These proteins are two isoforms of the same protein with the longer of the two being known as hnRNPB2. In this case both forms of the protein had a mutation in a highly conserved portion of the protein. The mutation consisted of an aspartate residue, located at D290 in hnRNPA2 and D302 in hnRNPB1, being replaced with a valine. In a previous study conducted by Dr. Eric Ross and James Toombs a prion propensity cart was created. According to this study the prion propensity of the original aspartate was 0.080, much lower than that of the new valine residue which scores a 0.81. Another contributing factor to the importance of this mutation is that it occurs within the C-terminal PrLD that is present in both proteins. The second mutation that this study followed was present in a similar protein

Molecular chaperones stabilize unfolded or misfolded proteins until native conformations have been obtained to promote cell survival during and after stress conditions. They do not change or add to the folding principles encoded by a protein because polypeptide chains inherently carry within them all the information that is necessary for achieving the native state of a protein. Instead, they optimize the folding process by stabilizing folding intermediates and are involved in every aspect of proteome maintenance including de novo folding, refolding of stress-induced misfolded proteins, and targeting proteins for degradation (Hartl 2009, Hartl 2011). Chaperones, many of which are induced or upregulated only during stress conditions, work in cooperative networks when protein-aggregate concentration