In a study published in the January 25, 2023 issue of Nature, Helen Wills Neuroscience Institute (HWNI) member James Hurley and colleagues describe the structure of a protein megacomplex that controls degradation of cell components. The megacomplex — formed through an interaction between the protein TFEB and the enzyme complex mTORC1 — regulates the formation of organelles called lysosomes that break down and recycle cellular components.
The study reveals how mTORC1 inactivates TFEB, reducing degradation of cell components, and identifies potential new targets for drugs to control the activity of TFEB. This could lead to the development of new therapeutics to treat neurodegenerative diseases such as Alzheimer’s and Parkinson’s, which involve accumulation of toxic proteins and debris, as well as drugs for cancer and other types of diseases.
To learn more, read the research briefing in Nature and the paper: Structure of the lysosomal mTORC1–TFEB–Rag–Ragulator megacomplex by Cui, Z., Napolitano, G., de Araujo, M.E.G. et al. (Nature, 2023).
This research was supported by Genentech as part of the Alliance for Therapies in Neuroscience (ATN) and the National Institute of General Medical Sciences, National Institutes of Health, grant no. R01 GM111730 to Hurley, as well as other support to his collaborators (see paper for details). The ATN is a research partnership established in 2021 between UC Berkeley, UC San Francisco, Genentech (a member of the Roche group), Roche, and the University of Washington.