R. Scott ProsserUniversity of Toronto Distinguished Professor of Biophysical Chemistry Ph.D.
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.
JBC472H and JCP422H (undergraduate), CHM1455F, BTC1710 (graduate)
Kim, T. H., Mehrabi, P., Ren, Z., Sljoka, A., Ing, C., Bezginov, A., Ye, L., Pomes, R., Prosser. R. S., and Pai, E. F.. The role of dimer asymmetry and protomer dynamics in enzyme catalysis. Science 355 (6322) Science
Staus, D. P., Strachan, R. T., Manglik, A., Pani, B., Kahsai, A. W., Kim, T. H., Wingler, L. M., Ahn, S., Chatterjee, A., Masoudi, A., Kruse, A. C., Pardon, E., Steyaert, J., Weis, W. I., Prosser, R. S., Kobilka, B. K., Costa, T., and Lefkowitz, R., J.. Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation.
Nature 535 (7612), 448-452 Nature
Ye, L., Van Eps, N., Zimmer, M., Ernst, O. P., and Prosser, R. S.. Activation of the A2A adenosine G-protein-coupled receptor by conformational selection. Nature 533 (7602), 265-268 Nature
Alvares, R. D. A., Lau, J. Y. C., Macdonald, P. M., Cunningham, C. H., and Prosser, R. S.. Direct quantitative 13C-filtered 1H magnetic resonance imaging of PEGylated biomacromolecules in vivo. Magnetic resonance in medicine. doi:10.1002/mrm.26237 PubMed
Alvares, R. D. A., Hasabnis, A., Prosser, R. S., and Macdonald, P. M.. Quantitative detection of PEGylated biomacromolecules in biological fluids by NMR. Analytical Chemistry 88 (7), 3730-3738 ACS Publications
Larda, S.T., Pichugin, D., and Prosser, R. S.. Site-specific labeling of protein lysine residues and N-terminal amino gruops with indoles and indole-derivatives. Bioconjugate Chemistry 26 (12), 2376-2383 ACS Publications
Manglik, A., Kim, T. H., Masureel, M., Altenbach, C., Yang, Z., Hilger, D., Kobilka, T. S., Thian, F. S., Hubbell*, W. L., Prosser, R. S.*, and Kobilka, B. K.* 2015 Structural insights into the dynamic process of β2-adrenergic receptor signaling. Cell 161, 1101-1111.* (Co-corresponding authors)
Ye, L., Larda, S. T., Feng, Y. Q., Manglik, A., and Prosser, R. S. 2015 A Comparison of Chemical Shift Sensitivity of Trifluoromethyl Tags – Optimizing Resolution in 19F NMR Studies of Proteins. J. Biomol. NMR 62, 97-103.
Prosser, R. S. and Kim, T. H. 2015 Nuts and Bolts of CF3 and CH3 NMR. Towards an Understanding of Conformational Exchange of GPCRs. Published in G-Protein-Coupled Receptors in Drug Discovery, in the lab protocol series Methods in Molecular Biology, Springer
Prosser, R. S. 2014 New Pipelines for Novel Allosteric GPCR Modulators. Biophys. J. 107, 287-288.
Hoang, J., and Prosser, R. S. 2014 Conformational Selection and Functional Dynamics of Calmodulin: A F-19 Nuclear Magnetic Resonance Study. Biochemistry 53, 36, 5727-5736.
Alvares, R., Gupta, S., Macdonald, P. M., and Prosser, R. S. 2014 Temperature and Pressure Based NMR Studies of Detergent Micelle Phase Equilibria. J. Phys. Chem. B 118, 5698-5706.
Nygaard, R., Zou, Y., Dror, R. O., Arlow, D. H., Pan, A. C., Liu, C. W., Fung, J. J., Bokoch, M. P., Mildorf, T. J., Thian, F. S., Kobilka, T. S., Shaw, D. E., Mueller, L., Prosser, R. S., and Kobilka, B. K. 2013. The dynamic process of β2 adrenergic receptor activation. Cell 152, 532-542.
Please visit http://sites.utm.utoronto.ca/prosserlab/content/publications for an up to date list of publications.