Fidelity and Regulation of Signal Recognition Particle

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Understanding the cellular ‘mail distribution’ system of newly synthesized proteins is of fundamental importance for understanding life itself and for harnessing and engineering organisms to solve societal needs such as food and clean energy. In addition to the basic understanding and support for societal needs, this project will provide excellent opportunities for science education and the associated challenges that emerged from the COVID-19 pandemic. The results of the research will be disseminated through publications in academic journals and presentations at scientific conferences, as well as lecture forums that directly interface with the general public. The education component of the project will emphasize the training of graduate students and postdoctoral scholars in multidisciplinary biochemical and biophysical research. It will also expose high school and undergraduate students to state-of-the-art research tools and provide leadership experience for the graduate students and postdocs. Finally, the project will generate valuable reagents, tools, and assays that are useful to many other researchers.Eukaryotic cells are highly compartmentalized, with each organelle harboring a unique set of proteins that endow the organelle its structure and functions. To maintain the higher order structure and proper functioning of the cell, all newly synthesized proteins need to localize to their correct cellular destinations. To accomplish this, cells have evolved a universally conserved protein targeting machine, signal recognition particle (SRP), to recognize and deliver newly synthesized proteins to the appropriate cellular membrane. This project aims to understand how SRP is regulated in the cell to ensure the organelle specificity of protein localization, and how its complex with the SRP receptor and the nascent protein is disassembled at the target membrane to allow efficient insertion of nascent proteins. The proposed project will combine the expertise of the Shan lab in mechanistic biochemistry and the Weiss lab in biophysics to decipher the sophisticated spatiotemporal regulation of SRP. The results will reveal generalization principles that ensure the proper functioning of the “mail delivery” system in the cell.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.