Rag GTPases
Table of Contents
Proteins that "sense" the protein levels and localize mTORC1 [1]. They are obligate protein heterodimers (RagA/B + RagC/D, binded by the CRD domain, each Rag GTPase has a C-terminal domain that have a conserved fold known as the roadblock domain [2]. They recruit mTOR to the lysosomal surface and activate it when amino acids are plentiful [2]. Rag heterodimers activate in presence of amino acids, and localize to the surface of the lysosome [1]. Rag A/B is regulated by the GATOR1 complex (nucleotide status).
GATOR1 complex / LAMTOR Ragulator complex:
- Activate Rag (RagA/BGTP - RagC/DGDP) in presence of amino acids.
- Localize Rag proteins to the surface of the lysosome (active state).
- Inactivate Rag (RagA/BGDP - RagC/DGTP) in absence of amino acids.
[1]
N. Alesi and E. P. Henske, “Keeping up with the rag GTPases,” Nat cell biol, vol. 24, no. 9, pp. 1330–1331, Sep. 2022, doi: 10.1038/s41556-022-00981-1. Available: https://www.nature.com/articles/s41556-022-00981-1. [Accessed: Nov. 03, 2025]
[2]
J. Cherfils, “Encoding allostery in mTOR signaling: The structure of the rag GTPase/ragulator complex,” Molecular cell, vol. 68, no. 5, pp. 823–824, Dec. 2017, doi: 10.1016/j.molcel.2017.11.027. Available: https://www.sciencedirect.com/science/article/pii/S1097276517308869. [Accessed: Nov. 03, 2025]