Structural basis for the docking of mTORC1 on the lysosomal surface
Abstract
The protein kinase mTORC1 controls cellular growth in response to external signals. In the presence of nutrients, it localizes on the surface of the lysosome, where it is activated. The Raptor domain of mTORC1 binds to a complex comprising the protein Ragulator and a heterodimer of the Rag guanosine triphosphatase, which can adopt four different nucleotide conformations depending on nutrient availability. Rogala et al. determined the structure of the Raptor-Rag-Ragulator complex at 3.2-angstrom resolution by cryo–electron microscopy. The structure shows why Raptor binds only to a specific nucleotide conformation of the Rag heterodimer and suggests a model for how mTORC1 would dock onto the lysosomal surface, which is a key step in its activation.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 25, 2019
- Source ID
- 10.1126/science.aay0166
Entities
People
- Alexia M S Bottino
- Ange-Célia Priso Fils
- Anna Niehaus
- Daan Overwijn
- Daniel Leary
- David M. Sabatini
- Edward J Brignole
- Jibril F Kedir
- Kacper B Rogala
- Laura F. Bianchi
- Monther Abu-Remaileh
- Nouf N Laqtom
- Rikke Dueholm
- Sherry X Zhou
- Xin Gu
Organizations
- American Cancer Society
- Broad Institute
- Charles A. King Trust
- Howard Hughes Medical Institute
- Koch Institute for Integrative Cancer Research at MIT
- Lustgarten Foundation for Pancreatic Cancer Research
- Massachusetts Institute of Technology
- National Institutes of Health
- Tuberous Sclerosis Association
- United States Department of Defense
- Whitehead Institute