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Proteins are important molecules that are needed for structure, function, and other vital processes in the cell. Proteins are synthesized by molecular machines called ribosomes, and they exit from ribosomes as chains of amino acids that must fold into their correct three-dimensional conformation in order to function properly. Newly synthesized proteins, however, are susceptible to misfolding during synthesis or after leaving the ribosome, leading to a loss of function, or even acquiring a new harmful function. Protein misfolding is associated with numerous neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. A class of misfolded proteins, known as prions, are self-propagating and can cause normally folded proteins of the same type to switch to the prion form. Saccharomyces cerevisiae, a species of yeast, has numerous proteins known to misfold and aggregate in a prion-like fashion. Ribosome-associated molecular chaperones are a class of proteins that help prevent the misfolding of other proteins. For example, the chaperones Zuo1 and Ssz1 form a dimeric ribosome-associated complex (RAC) on yeast ribosomes. Previous work in the Cameron lab has shown that the RAC is critical for proper folding of newly synthesized proteins and is able to suppress prion formation in yeast. Due to a notable degree of conservation of the cellular protein synthesis machinery among all organisms, the function of the Ssb/RAC complex may be conserved from yeast to humans. Thus, we hypothesized that the human homologs of the yeast RAC components may behave similarly to RAC in yeast cells. To study this, we transformed yeast lacking the RAC components Zuo1 and Ssz1 and expressing the human forms of these chaperones. We found that yeast with human RAC showed higher growth than yeast lacking both components. Future research will statistically explore whether, similarly to the yeast counterparts, human RAC can suppress prion formation in yeast.
Terrenzio, Danielle; Marley, Amanda; Kim, Seongchan; and Fandino Pachon, Nikole, "Can the Yeast Ribosome-Associated Complex Chaperones Zuo1 and Ssz1 be Functionally Replaced With Their Human Homologs Mpp11 and Hsp70L1?" (2021). Biology Presentations. 30.
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