UC Davis

Protein systems that do not obey the “one protein, one fold” principle, as is increasingly seen across the biological sciences, are implicated in a wide range of functional and misfunctional processes. This dissertation describes characterizations of such protein systems. Intrinsically disordered proteins that retain dynamic interconversion and rapidly sample a variety of conformations are studied, chapters 2 and 5. In addition, amyloid forming proteins that undergo conformational selection into multiple, distinct amyloid folds are characterized, chapters 3, 4, and 5. Solution and solid state nuclear magnetic resonance, NMR, is the key technique used, along with additional biophysical techniques. NMR is particularly well suited to the study of these two protein classes, disordered and amyloid, because their inherent structural plasticity, or inherent amyloid “clumping” behavior, leads to these protein types often being non-amenable to study by traditional structural biology techniques, x-ray crystallography or cryogenic electron microscopy. The results presented aid in the understanding of: protein transcription factors PHL4, chapter 2, and TDP43, chapter 4 and 5, as well as the intermediate filament protein Tm1’s alternative isoform in Drosophila, chapter 3.