Consequences of Protein Misfolding
Topic: Protein Folding and Molecular Chaperones - What happens when proteins fold incorrectly?
Consequences of Protein Misfolding
Vina Ong
20554965
Section: 126
Ares Rao A protein is made of amino acids that supply cells with their formation and execute most of their activities. Proteins can easily be denatured and refolded which happens spontaneously as the denaturing solvent is added and removed, under the proper circumstances. (Alberts, 2014) Since they can be easily denatured there is always a chance of misfolding, which can induce aggregates rather than refolding to its original shape. Misfolding of proteins affect the way proteins function and are associated with serious diseases. Any mutation that affects the sequence, whether it be a missing or incorrect amino acid can lead to protein misfolding. Denaturation of proteins happen when the hydrogen bonds, ionic bonds, and disulphide bridges are disrupted while maintaining a proteins shape. These bonds can be disrupted easily when the protein is exposed to a high concentration of solvent under proper conditions. Urea for example, causes the protein to denature. But, after the removal of urea, the protein refolds into its original shape. (Albert, 2014) The denature and renature of proteins often works best in small proteins, where the amino acid sequence is shorter. This lowers the chance for the protein to misfold. This is not always the case however as, there are a multitude of different chain lengths, which creates a larger opportunity for misfolding to occur. During denaturation, instead of refolding into its original conformation, aggregates of protein such as amyloid fibrils, can be induced. (Lin, 2013) Amyloid fibrils are insoluble and toxic to cells. (Morgan, 2012) Sediments of amyloid fibrils are found within organs and tissues and are prone to be fibrous and extracellular. They are capable of accumulating the tissue in a disease. Amyloid fibrils take on a ß-sheet conformation
Consequences of Protein Misfolding
Vina Ong
20554965
Section: 126
Ares Rao A protein is made of amino acids that supply cells with their formation and execute most of their activities. Proteins can easily be denatured and refolded which happens spontaneously as the denaturing solvent is added and removed, under the proper circumstances. (Alberts, 2014) Since they can be easily denatured there is always a chance of misfolding, which can induce aggregates rather than refolding to its original shape. Misfolding of proteins affect the way proteins function and are associated with serious diseases. Any mutation that affects the sequence, whether it be a missing or incorrect amino acid can lead to protein misfolding. Denaturation of proteins happen when the hydrogen bonds, ionic bonds, and disulphide bridges are disrupted while maintaining a proteins shape. These bonds can be disrupted easily when the protein is exposed to a high concentration of solvent under proper conditions. Urea for example, causes the protein to denature. But, after the removal of urea, the protein refolds into its original shape. (Albert, 2014) The denature and renature of proteins often works best in small proteins, where the amino acid sequence is shorter. This lowers the chance for the protein to misfold. This is not always the case however as, there are a multitude of different chain lengths, which creates a larger opportunity for misfolding to occur. During denaturation, instead of refolding into its original conformation, aggregates of protein such as amyloid fibrils, can be induced. (Lin, 2013) Amyloid fibrils are insoluble and toxic to cells. (Morgan, 2012) Sediments of amyloid fibrils are found within organs and tissues and are prone to be fibrous and extracellular. They are capable of accumulating the tissue in a disease. Amyloid fibrils take on a ß-sheet conformation
References: Alberts et al, B. (2014). Macromolecules in Cells. In Essential Cell Biology (Fourth ed., pp. 126-142). New York: Garland Science. Lin, Y., Lee, Y., Yoshimura Y., Yagi H., Goto Y. (2013). Solubility and supersaturation-dependent protein misfolding revealed by ultrasonication. Langmuir, 30, 1845-1854. DOI: 10.1021/la403100h Morgan, G., & Radford, S. (2012). How Proteins Fold and Misfold. In Protein Folding and Misfolding: Shining Light by Infrared (pp. 1-3). Berlin: Springer-Verlag Berlin Heidelburg. DOI: 10.1007/978-3-642-22230-6 Rambaran, R., & Serpell, L. (2008). Amyloid Fibrils. Prion, 2(3), 112-117