6B9X

Crystal structure of Ragulator

Summary for 6B9X

• Entry DOI: 10.2210/pdb6b9x/pdb
• Descriptor: Ragulator complex protein LAMTOR1, Ragulator complex protein LAMTOR2, Ragulator complex protein LAMTOR3, ... (6 entities in total)
• Functional Keywords: ragulator, lamtor, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Late endosome membrane; Lipid-anchor; Cytoplasmic side: Q6IAA8; Late endosome membrane ; Peripheral membrane protein ; Cytoplasmic side : Q9Y2Q5 Q9UHA4; Lysosome : Q0VGL1
• Total number of polymer chains: 5
• Total formula weight: 73920.74

Authors

SU, M.-Y.,Hurley, J.H. (deposition date: 2017-10-11, release date: 2017-11-08, Last modification date: 2023-10-04)

Primary citation

Su, M.Y.,Morris, K.L.,Kim, D.J.,Fu, Y.,Lawrence, R.,Stjepanovic, G.,Zoncu, R.,Hurley, J.H.
Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex.
Mol. Cell, 68:835-846.e3, 2017

PubMed Abstract: The lysosomal membrane is the locus for sensing cellular nutrient levels, which are transduced to mTORC1 via the Rag GTPases and the Ragulator complex. The crystal structure of the five-subunit human Ragulator at 1.4 Å resolution was determined. Lamtor1 wraps around the other four subunits to stabilize the assembly. The Lamtor2:Lamtor3 dimer stacks upon Lamtor4:Lamtor5 to create a platform for Rag binding. Hydrogen-deuterium exchange was used to map the Rag binding site to the outer face of the Lamtor2:Lamtor3 dimer and to the N-terminal intrinsically disordered region of Lamtor1. EM was used to reconstruct the assembly of the full-length RagA:RagC dimer bound to Ragulator at 16 Å resolution, revealing that the G-domains of the Rags project away from the Ragulator core. The combined structural model shows how Ragulator functions as a platform for the presentation of active Rags for mTORC1 recruitment, and might suggest an unconventional mechanism for Rag GEF activity.

PubMed: 29107538
DOI: 10.1016/j.molcel.2017.10.016

Experimental method

X-RAY DIFFRACTION (1.42 Å)