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. Author manuscript; available in PMC: 2023 May 19.
Published in final edited form as: Mol Cell. 2022 Mar 25;82(10):1836–1849.e5. doi: 10.1016/j.molcel.2022.03.002

Figure 6. Conformation of the Rag GTPases in the inhibitory mode and in the GAP mode.

Figure 6.

A. The Rag GTPase heterodimer adopts different conformations upon binding to upstream regulators or downstream effectors..

B. Summary of the conformational parameters for Rag GTPases at different states in panel A.

C. Multiple turnover GTP hydrolysis assay stimulated by GATOR1[DEPDC5(Y775A)].

D. Thermodynamic cycle for GATOR1 and nucleotide binding to the Rag GTPase heterodimer.

E. Hypothetical in vivo binding of two copies of the Rag-Ragulator complex on the lysosomal membrane to GATOR1.

F. Relative orientation of GATOR1 to the lysosomal membrane dictates its GAP function. In the inhibitory mode, Arg78 of NPRL2 localizes away from the lysosomal surface.