The Role of Protein Folding and Misfolding in Cells

The Role of Protein Folding and Misfolding in Cells

Abstract

Due to protein misfolding normal cells undergo mutations which can lead to a cell expression a completely different characteristic that it's normal counterparts. In some cases the mutation is so severe that the entire cell dies. Lucky cell have two systems (chaperones and proteasome) which are in charge of ensuring that proteins are folded correctly. Chaperones improve a proteins likelihood of successful folding while proteasomes destroy improperly folded protein back into their amino acid sequences. Even with these systems some protein misfolding inevitable happens and produces diseases such as Huntington's, Alzheimer's, and Cancer. Recent studies in biotechnology have come with hopefully a break through; in which proteins can be synthesized and inserted to correct some areas of protein misfolding; resulting in better treatment of diseases. Multiple authors and researchers have agreed that in order to understand cause of protein misfolding; the reason as to why proteins are coded for specific shapes must be discovered. In the future, synthetic proteins will not only lead to better treatments, but probably lead to important discoveries of protein misfolding

Literature Review

Protein folding is an essential process to every cell in an organism; considering that genetic expression for the majority comes from proteins. It is currently unknown how a protein establishes its shape, how the shape is maintained, and why the amino acid sequences of proteins codes for a specific shape. These instances of unknown are each part of the protein folding problem, which has troubled researchers for nearly a century(Thusber 2010). So what does a protein actually do? Well proteins have a wide variety of functions within cells and within the body as a whole; some include; repairing of tissue, production of hormones and enzymes, and basically keeping the body healthy (Benardot 2005). When proper protein folding occurs a protein will function like any other; but sometimes during the replication of DNA to mRNA and then to tRNA proteins tend to either undergo some type of error resulting in a mutation; the most commonly known are missense, nonsense, silent, and insertion and deletion mutation (Thusberg 2010). The most common type of mutation; missense; occurs when a codon of an amino acid is alter which changes the amino acid into a completely different one. This mutation has the ability to affect the structure and function of a protein, resulting in a possible inexpression of a gene(s). Nonsense mutations drastically affect genes. They are the results of a codon with an amino acid being change to a stop codon; which shorten the amino acid chain of the resulting protein. Nonsense mutation can lead to nonsense mediated decay, where mRNA decays because there is not a gene product. Silent mutations and surprising exactly what they sound like; usually the third amino acid of a codon is altered, but the altered from doesn't affect the protein produced. These mutations don't cause a huge gene variation, but may cause subtle changes in protein folding.

Proteins usually fold into diverse complex shapes, which allows from the protein to perform many jobs in a cell. Protein folding is a very intricate process which on occasion doesn't always go as planned. Protein misfolding occurs either because a mutation which changes an amino acid making it hard for a protein to fold correctly has been inherited; sometimes a mistake is made between coping DNA into mRNA. Scientists estimate that this occurs in 1 out of every 7 proteins; and even if everything goes correctly when forming the protein it may not fold properly (Geiler 2010). The inside of the cell such as temperature and pH also effects whether or not proteins fold properly. Protein misfolding is the known cause for numerous diseases. When the proteins of a cell do not fold correctly there are two different problems that occur. The first is a lack of the needed folded version of the protein which leads to not enough protein to carry out a function; this is called loss of function. For example; a protein may be coded to break down toxin within a cell; the cell would eventually have a build up a toxin and inevitably die with the proper folded protein (Gielor 2010). Diseases such as Tay-Sachs disease, cystic fibrosis, and cancer all result from the lack of enough of one protein. Goes to show just how important one protein can be. Proteins that misfold may also deteriorate the health of the cell no matter what the function. A protein is coded for a specific shape in order to fit into a cell, but if its coded wrong then the shape may cause multiple misfolded proteins to stick together called aggregates (Dill2012). Scientists believe that diseases such as Parkinson's, Huntington's, and Alzheimer's are the result of proteins sticks to each other. Research shows that protein misfolding occurs many times in a cell. Cells are used