Protein dynamics: from the marginally to the extremely stable

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We live in a world where the environment is becoming more extreme, and yet much remains to be learned about how organisms successfully adapt to extreme conditions. Dehydration, high pressure, temperature changes are all variables that resilient organisms can cope with to survive, and proteins play a particularly important role. This research project looks at how some proteins protect other proteins when the temperature goes up too high for survival, how proteins that are barely able to fold can fold in the right environment, and how microorganisms that live at high pressures and temperatures cope by harnessing the adaptability of proteins critical for survival. This project will support the training of high school, undergraduate, graduate, and post-graduate researchers on state-of-the-art techniques and instruments, helping the nation be prepared with qualified scientists who can solve problems at every level when we encounter our own extreme scenarios.This project, focused on protein dynamics inside living cells and organisms, has the goal of understanding how protein evolution optimizes flexibility, develops novel structure and function, and adapts proteins to subtle differences even between different cell types in a single organism. This will be accomplished through three distinct but related subprojects. A class of intrinsically disordered proteins with low charge/hydropathy ratio will be studied to determine if quinary structure and crowding in cells may be sufficient to induce structure. Using zebrafish as a model organism, heat shock chaperoning will be studied in vivo to determine how protein-chaperone interactions can be differentiated in different tissues. Extremophiles tune the native state fluctuations of enzymes to allow function under a wide range of temperatures, pressures, and other solvent variables. To elucidate how organisms tune the phase diagrams of their proteins to maximize function, experiments and simulations will be conducted on enzyme phosphoglycerate kinase from eight different mesophilic and extremophilic organisms covering a wide range of environments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.