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Proteins are one of the four main biological macromolecules that are central to life. Proteins are involved in a multitude of functions, such as cell signaling, intracellular regulation, and biochemical catalysis. These varying functions are determined by a protein’s complex three-dimensional shape. As a result, the misfolding of a protein can lead to a loss of intrinsic function. In prion or prion-like mechanisms, a misfolded protein can self-propagate to other correctly folded proteins, leading to protein aggregation and cellular damage that is characteristic of many mammalian diseases, such as Creutzfeldt-Jakob disease in humans. One factor that has been suggested to increase misfolding of certain proteins is translational stalling, a process in which the cell’s protein synthesis machinery, the ribosome, will slow down or stop, allowing nascent proteins to adopt alternate conformations. In S. cerevisiae, translational stalling exists as a natural regulatory mechanism to maintain proteostasis, but certain factors may further encourage translational pausing. One of these factors is proteotoxic stress, which is characterized volumes of misfolded proteins beyond the capability of the cell’s degradation machinery. Using prolonged heat shock and the arginine analog canavanine, both of which are known to cause proteotoxic stress, to halt the synthesis of two proteins with known misfolded structures, we may shed light on the mechanism and rate of spontaneous prion formation as cells maintain the delicate balance of survival.
Janik, Steven, "Proteotoxic Stress-induced Ribosome Stalling Does Not Significantly Impact Spontaneous Prion Formation of Sup35 or Poly-glutamine in Saccharomyces cerevisiae" (2023). Biology Summer Fellows. 101.
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