Scott Prosser

R. Scott Prosser

University of Toronto Distinguished Professor of Biophysical Chemistry
Ph.D.

Research Profile:

Prosser Research Picture

Our research focuses on dynamics and mechanism of complex biological processes such as: 1) protein folding, 2) protein misfolding and amyloidosis, 3) enzyme functional dynamics, 4) GPCR functional dynamics, and 5) Direct molecular imaging of proteins and nanoparticles by MRI.  In many cases, we make use of 19F or 13C,1H NMR to detect subtle low-lying states within an ensemble, and piece together a mechanistic description. 19F NMR chemical shifts are exquisitely sensitive to molecular environments. Thus, subtle differences in conformation, folding intermediates, or different aggregation states are more likely to be resolved by 19F NMR than by other methods.

Receptors and amyloid systems represent a tremendous challenge in part because of the need for high yield expression expression of functional protein with appropriate post translational modifications. We have focused in recent years on perfecting expression in yeast which has created new opportunities for the study of conformational equilibria, dynamics, activation mechanisms, and functional pathways of complex proteins.

Courses Taught:

CHM372H, JBC472H and JCP422H  (undergraduate); CHM1455F and BTC1710  (graduate)

Publications

Camila Botin Francisco, Cleverton de Souza Fernandes, Fernanda Franco Dourado, Gisele de Freitas Gauze, Roberto Rittner, Robert Scott Prosser, and Ernani Abicht Basso. 2024. Conformational Landscape of α‑Halopropiophenones Determined by n J C–H NMR Reveals Unexpected Patterns and Geometric Constraints. J. Phys. Chem. A 128, 1566-1575. https://doi.org/10.1021/acs.jpca.3c06934

Geordon A. Frere, Advait Hasabnis, Camila B. Francisco, Motasem Suleiman, Olga Alimowska, Rima Rahmatullah, Jerome Gould, Celia Yi-Chia Su, Oleksandr Voznyy, Patrick T. Gunning, Ernani A. Basso, and Robert S. Prosser. 2024. Next-Generation Tags for Fluorine Nuclear Magnetic Resonance: Designing Amplification of Chemical Shift Sensitivity. J. Am. Chem. Soc. https://doi.org/10.1021/jacs.3c09730

Jerry Augustine, Karina A. Baksh, Robert Scott Prosser, and Deborah B. Zamble. 2023. Insights into the Allosteric Response to Acidity by the Helicobacter pylori NikR Transcription Factor. Biochemistry 62 (22) 3265-3275 https://doi-org.myaccess.library.utoronto.ca/10.1021/acs.biochem.3c00356

R. Scott Prosser. 2023. A beginner's guide to 19F NMR and its role in drug screening. Can. J. Chem. 101(10) 758-764. https://doi10.1139/cjc-2023-0028

R. Scott Prosser and Nicholas A. Alonzi. 2023. Discerning conformational dynamics and binding kinetics of GPCRs by 19F NMR. Current Opinion in Pharmacology 72:102377. https://doi: 10.1016/j.coph.2023.102377

Shuya Kate Huang, Rima Rahmatullah, Aditya Pandey, Ned Van Eps, Roger Sunahara, Oliver P. Ernst and Robert Scott Prosser. 2023. Mapping the conformational landscape of the stimulatory heterotrimeric G protein. Nature Structural and Molecular Biology 30 502-511. https://www.nature.com/articles/s41594-023-00957-1

Karina A. Baksh, Jerry Augustine, Adnan Sljoka, Robert Scott Prosser, and Deborah B. Zamble. 2023. Mechanistic insights into the allosteric response in the Helicobacter pylori NikR metalloregulator. Journal of Biological Chemistry 299 102785 https://doi.org/10.1016/j.jbc.2022.102785

Shuya Kate Huang and Robert Scott Prosser 2022. Dynamics and mechanistic underpinnings to pharmacology of class A GPCRs: an NMR perspective. American Journal of Physiology, 322: C739-C753. https://doi.org/10/1152/ajpcell.00044.2022

Shuya Kate Huang, Omar Almurad, Reizel J Pejana, Zachary A Morrison, Aditya Pandey, Louis-Philippine Picard, Mark Nitz, Adnan Sljoka, and Robert Scott Prosser 2022. Allosteric modulation of the adenosine A2A receptor by cholesterol. ELife 2022; 11:e73901 doi: 10.7554/eLife,73901

Overduin, M., Trieber, C. Prosser, R. S., Picard, L., and Sheff, J.G. 2021. Structures and Dynamics of Native-State Transmembrane Protein Targets and Bound Lipids. Membranes. 11(6) 451; https://doi.org/10.3309/membranes11060451.

Picard, L., and Prosser, R. S. 2021. Advances in the Study of GPCRs by 19F NMR Corr. Opin. Structural Biology, Vol 69, 169-179

Fere, G., Pandey, A., Gould, J., Hasabnis, A., Gunning, P. T. and Prosser, R. S. 2022. The Application of 19F NMR to Studies of Protein Function and Drug Screening. In GPCR as Therapeutic targets. A Gilchrist (ed.), John Wiley and Sons Publishing Hoboken, NJ.

Fernandes, D. D., Neale, C. Gomes, G. W., Li, Y., Malik, A., Pandey, A., Orazietti, A. P., Wang, X., Ye, L., Prosser, R. S., and Gradinaru, C. (2021). Ligand modulation of the conformational dynamics of the A2A adenosine receptor revealed by single-molecule fluorescence. Scientific Reports 11, 5910 (1-16).

Huang, S. K.; Pandey, A.; Tran, D. P.; Villanueva, N. L.; Kitao, A.; Sunahara, R. K.; Sljoka, A.; Prosser, R. S. (2021). Delineating the conformational landscape of the adenosine A2A receptor during G protein coupling. Cell 184, 1-11.

Baksh, K. A., Pichugin, D., Prosser, R. S., & Zamble, D. B. (2021). Allosteric regulation of the nickel-responsive NikR transcription factor from Helicobacter pylori. Journal of Biological Chemistry, 296, 100069.

Prosser, R. S. & Taverner, K. (2020). Water Networks and Allosteric Scaffolds ‐ What Does Water Have to do with Protein Dynamics? The Journal of the Federation of American Societies for Experimental Biology, 34(1). https://doi.org/10.1096/fasebj.2020.34.s1.09500.

Fernandes, D. D., Neale, C., Gomes, G. W., Li, Y., Pandey, A., Ye, L., Prosser, R. S. & Gradinaru, C. C. (2020). Dynamic Fingerprinting of the A2A Adenosine Receptor in Different Ligand-biased States. Biophysical Journal, 118(3), 178a.

Fernandes, D.D., Neale, C., Gomes, G.N.W., Li, Y., Malik, A., Pandey, A., Orazietti, A., Wang, X., Ye, L., Prosser, R.S. & Gradinaru, C.C. (2020). Ligand Modulation of the Conformational Dynamics of the A2A Adenosine Receptor Revealed by Single-Molecule Fluorescence. bioRxiv.

Prosser, R. S. (2020). Tailor-made GPCRs. Nature chemical biology, 16(1), 5-6.

Pandey, A., Larda, S. T., La Plante, S. & Prosser, R. S. (2020). NMR-based approaches to the study of GPCRs and GPCR-ligand interactions. GPCRs Structure, Function, and Drug Discovery, 65-80. https://doi.org/10.1016/B978-0-12-816228-6.00004-0.

Staus, D. P., Wingler, L. M., Pichugin, D., Prosser, R. S., & Lefkowitz, R. J. (2019). Detergent-and phospholipid-based reconstitution systems have differential effects on constitutive activity of G-protein–coupled receptors. Journal of Biological Chemistry, 294(36), 13218-13223.

Di Pietrantonio, C., Taverner, K., Mehrabi, P., Kim, T. H., Sljoka, A., Ing, C., ... & Prosser, R. S. (2019). Substrate-based Allosteric Regulation of a Homodimeric Enzyme. Protein Science (Vol. 28, pp. 204-204). 111 River St., Hoboken 07030-5774, NJ USA: WILEY.

Mehrabi, P., Di Pietrantonio, C., Kim, T. H., Sljoka, A., Taverner, K., Ing, C., ... & Prosser, R. S. (2019). Substrate-based allosteric regulation of a homodimeric enzyme. Journal of the American Chemical Society, 141(29), 11540-11556.

Di Pietrantonio, C., Pandey, A., Gould, J., Hasabnis, A., & Prosser, R. S. (2019). Understanding Protein Function Through an Ensemble Description: Characterization States by 19F NMR of Functional. Biological NMR Part B, 103.

Ye, L., Neale, C., Sljoka, A., Lyda, B., Pichugin, D., Tsuchimura, N., ... & Prosser, R. S. (2018). Mechanistic insights into allosteric regulation of the A 2A adenosine G protein-coupled receptor by physiological cations. Nature communications, 9(1), 1-13.

Huang, S. K., Ye, L., & Prosser, R. S. (2018). Characterizing GPCR Allostery by NMR Spectroscopy. Biophysical Journal, 114(3), 238a-239a.

Ye, L., Orazietti, A. P., Pandey, A., & Prosser, R. S. (2018). High-efficiency expression of yeast-derived G-protein coupled receptors and 19 F labeling for dynamical studies. In Protein NMR (pp. 407-421). Humana Press, New York, NY.

Ye, L., Van Eps, N., Li, X., Ernst, O. P., & Prosser, R. S. (2017). Utilizing tagged paramagnetic shift reagents to monitor protein dynamics by NMR. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 1865(11), 1555-1563.

Prosser, R. S., Ye, L., Pandey, A., & Orazietti, A. (2017). Activation processes in ligand‐activated G protein‐coupled receptors: A case study of the adenosine A2A receptor. Bioessays, 39(9), 1700072.

Alvares, R. D., Gautam, A., Prosser, R. S., van Veggel, F. C., & Macdonald, P. M. (2017). Shell versus Core Dy3+ Contributions to NMR Water Relaxation in Sodium Lanthanide Fluoride Core–Shell Nanoparticles. An Investigation Using O-17 and H-1 NMR. The Journal of Physical Chemistry C, 121(32), 17552-17558.

Alvares, R. D., Lau, J. Y., Macdonald, P. M., Cunningham, C. H., & Prosser, R. S. (2017). Direct quantitative 13C‐filtered 1H magnetic resonance imaging of PEGylated biomacromolecules in vivo. Magnetic resonance in medicine, 77(4), 1553-1561.

Brea, R. J., Cole, C. M., Lyda, B. R., Ye, L., Prosser, R. S., Sunahara, R. K., & Devaraj, N. K. (2017). In situ reconstitution of the adenosine A2A receptor in spontaneously formed synthetic liposomes. Journal of the American Chemical Society, 139(10), 3607-3610.

Fernandes, D. D., Ye, L., Li, Y., Zhang, Z., Gomes, G. N., Prosser, R. S., & Gradinaru, C. C. (2017). The Role of G-Protein-Coupled Receptor Activation by Conformational Selection as Revealed by Single-Molecule Fluorescence. Biophysical Journal, 112(3), 327a-328a.

Kim, T. H., Mehrabi, P., Ren, Z., Sljoka, A., Ing, C., Bezginov, A., Ye, L., Pomès, R., Prosser, R. S. & Pai, E. F. (2017). The role of dimer asymmetry and protomer dynamics in enzyme catalysis. Science, 355(6322).

Ye, L., Van Eps, N., Li, X., Ernst, O. P, & Prosser, R. S. (2017). Utilizing tagged paramagnetic shift reagents to monitor protein dynamics by NMR Proteins and proteomics. Biochimica et biophysica acta, 1865, 1555-1563. doi: 10.1016/j.bbapap.2017.09.011.

Naugler, D. G., & Prosser, R. S. (2017). Notes on Synthesis of perdeutero-5-13C, 5, 5, 5-trifluoroisoleucine VI. BioRxiv, 140681.