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Biochemistry & Molecular Biology
Proteins are important molecules that are needed for structure, function, and other important 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 loss of function of a protein. Protein misfolding is associated with numerous neurodegenerative diseases such as cystic fibrosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. A class of misfolded proteins, known as prions, are self-propagating and can be transmitted infectiously. They are associated with neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs). These include Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), and kuru in humans. 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 Ssz1p and Zuo1 form a dimeric ribosome-associated complex (RAC) on yeast ribosomes. The RAC, along with the chaperone Ssb1/2p, combine to form a chaperone triad that is critical for proper folding of newly synthesized proteins. 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. We are using S. cerevisiae to explore the function of yeast and human RAC.
Ahmed, Yusef G., "Can the Yeast Ribosome-Associated Complex Chaperones Zuo1 and Ssz1 be Functionally Replaced With Their Human Homologs Mpp11 and Hsp70L1?" (2017). Biochemistry and Molecular Biology Summer Fellows. 10.