Are Mussels and Legumes Really Odd Bedfellows? An Investigation into the Liquid-Liquid Phase Separation of Proline-Rich Proteins
Protein liquid-liquid phase separation is a functional step in many biological processes, from cellular stress survival strategies (1) to mussel byssus formation (2). There is still much to understand about the driving forces of phase separation and the roles it plays. I hope to delve deeper into the relationship between amino acid sequences and protein phase behavior by studying the liquid-liquid phase separation of mussel foot protein 1 (mfp-1) in the formation of marine mussel cuticles.
I will be using both in silico simulations and in vitro studies to compare mfp-1 to proteins from different organisms with high sequence similarity to mfp-1, such as cell wall proline-rich proteins (PRP) in plants. And from these experiments, I can draw predictions for the drivers of phase separation. Finding these drivers could give us insight into the function of similar protein sequences across many biological systems. This research is also highly applicable to biomedical technologies, as phase separation contributes critically to normal cell processes such as division*, as well as being a potential driver for many diseases (3). And mussel cuticles themselves have been shown to possess fascinating adhesive and protectively coating properties that can and are used to inspire the synthesis of new materials (4).
* centrioles are thought to be LLPS proteins
1. Franzmann, T. M., & Alberti, S. (2019). Protein Phase Separation as a Stress Survival Strategy. Cold Spring Harbor Perspectives in Biology, 11(6). doi:10.1101/cshperspect.a034058
2. Jehle, F., Macías-Sánchez, E., Sviben, S., Fratzl, P., Bertinetti, L., & Harrington, M. J. (2020). Hierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases. Nature Communications, 11(1). doi:10.1038/s41467-020-14709-y
3. Shin, Y., & Brangwynne, C. P. (2017). Liquid phase condensation in cell physiology and disease. Science, 357(6357). doi:10.1126/science.aaf4382
4. Guo, Q., Chen, J., Wang, J., Zeng, H., & Yu, J. (2020). Recent progress in synthesis and application of mussel-inspired adhesives. Nanoscale, 12(3), 1307-1324. doi:10.1039/c9nr09780e