Proteins must adopt the correct folded structure for full functionality. For some proteins, post-translational modifications have a tremendous impact on both the structure and the function of the protein. Structural regulatory control of protein function has been well established in many facets of biology and is often a key control step in signal transduction events that are essential for life, such as the response to nutrients and stresses, cell cycle progression, and proliferation. However, unexpected alterations in protein structure can be detrimental. Misfolded proteins are frequently associated with irreversible loss-of-function and disease instead of regulation. In this project, one group of proteins will be investigated for their ability to adopt a specific type of "misfolded" state (prion conformation) as a means of regulation. A group of prion proteins may have evolved with the intrinsic ability to produce major changes in conformation as a means of regulation of a central process essential for life: protein synthesis. Interestingly, a complex network of prion proteins may regulate protein synthesis in yeast. This research will focus on elucidating the underlying mechanistic principles of this type of regulation. The broader impact of this CAREER project will include training of undergraduate students in prion biology, as well as inclusion of under-represented minority high school students in the research project.
