Architecture of human Rag GTPase heterodimers and their complex with mTORC1
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) is known as the master kinase, acknowledging its key role in integrating multiple signals to regulate cell growth. When nutrients are abundant, heterodimers of Rag, a class of small guanosine triphosphatase, bind to mTORC1 and recruit it to the lysosome. Here, other signaling pathways converge on the mTORC1 complex. Anandapadamanaban et al. determined cryo–electron microscopy and crystal structures of a RagA/RagC heterodimer. The structures, together with dynamic studies, explain the nucleotide states required for binding to mTORC1 and support a mechanism for conformational communication between the RagA and RagC subunits in the heterodimer. RagA/RagC binding causes no conformational change in mTORC1, which is consistent with the idea that mTORC1 must sense additional growth regulators before it is activated.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 11, 2019
- Source ID
- 10.1126/science.aax3939
Entities
People
- Alex Berndt
- Balaji Santhanam
- Christopher M Johnson
- David M. Sabatini
- Glenn R Masson
- Jonathan Kaufman
- Kacper B Rogala
- Madhanagopal Anandapadamanaban
- Olga Perisic
- Roger L. Williams
Organizations
- American Cancer Society
- Broad Institute
- Cancer Research UK
- European Molecular Biology Organization
- Federation of European Biochemical Societies
- Howard Hughes Medical Institute
- Koch Institute for Integrative Cancer Research at MIT
- Laboratory of Molecular Biology
- Lustgarten Foundation for Pancreatic Cancer Research
- Massachusetts Institute of Technology
- Medical Research Council
- National Institutes of Health
- Royal Society of Chemistry
- The Company of Biologists
- Tuberous Sclerosis Association
- United States Department of Defense
- Whitehead Institute