Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.01.05.522916v1?rss=1

Authors: McSwiggen, D. T., Liu, H., Tan, R., Agramunt Puig, S., Akella, L. B., Berman, R., Bretan, M., Chen, H., Darzacq, X., Ford, K., Godbey, R., Gonzalez, E., Hanuka, A., Heckert, A., Ho, J. J., Johnson, S. L., Kelso, R., Klammer, A., Li, J., Lin, K., Margolin, B., McNamara, P., Meyer, L., Pierce, S. E., Sule, A., Tang, Y., Anderson, D. J., Beck, H.

Abstract:
The regulation of cell physiology largely depends upon intracellular interactions of functionally distinct proteins that act in combination. These interactions, which are often transient in nature, help to define the motion profiles of proteins. Measurement of protein motion within a living cellular environment will enable dissection of key interactions among proteins, however, attempts to measure protein motion are typically limited by the low spatial and temporal resolution of existing experimental platforms. Here, we describe a high-throughput single-molecule imaging platform that measures protein motion in living cells. We demonstrate the application of this platform by studying the dynamics of steroid hormone receptors and explore the pharmacology of compounds that affect estrogen receptor (ER) activity. Using our high-throughput single-molecule tracking (htSMT) platform, we screened 5,067 bioactive molecules, identifying multiple proteins and signaling pathways which perturb ER dynamics. We further deployed htSMT to characterize the impact of known ER modulators on ER protein dynamics, uncovering a correlation between ER dynamics and the ability of ER antagonists to suppress cancer cell growth. SMT provides a novel platform capable of measuring real-time target engagement within the living cellular environment. Our results support the view that this tool will prove uniquely valuable in measuring the dynamic interactions among proteins and will prove powerful for the identification of novel therapeutics.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC