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Johns Hopkins Chemistry Seminars–Fibrillization and Liquid-Liquid Phase Separation of the Tau Peptide

Joan-Emma Shea

University of California, Santa Barbara

Intrinsically disordered peptides (IDP) are a special class of proteins that do not fold to a unique three-dimensional shape. These proteins play important roles in the cell, from signaling to serving as structural scaffolds. Under pathological conditions, they can self-assemble into structures that are toxic to the cell, and a number of neurodegenerative diseases are associated with this self-assembly process. My talk will focus on the Tau protein, an IDP that binds to microtubules and can form fibrillar aggregates, a process that has been linked with Alzheimer’s disease. In addition to forming fibrils, the Tau protein can also phase separate into a protein rich and a protein depleted phase, a process known as liquid-liquid phase separation (LLPS). This process may play a protective role in the cell against pathological fibrillization. I will present molecular dynamics and field theoretic simulations that map out the phase diagram for Tau LLPS, and use this phase diagram to predict the conditions under which Tau can be driven towards LLPS under live cell coculturing conditions.