5Y3A

Crystal structure of Ragulator complex (p18 49-161)

Summary for 5Y3A

• Entry DOI: 10.2210/pdb5y3a/pdb
• Related: 5Y38 5Y39
• Descriptor: Ragulator complex protein LAMTOR1, Ragulator complex protein LAMTOR2, Ragulator complex protein LAMTOR3, ... (7 entities in total)
• Functional Keywords: ragulator complex, 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; Cytoplasm: O43504
• Total number of polymer chains: 10
• Total formula weight: 121714.51

Authors

Zhang, T.,Ding, J. (deposition date: 2017-07-28, release date: 2017-12-27, Last modification date: 2023-11-22)

Primary citation

Zhang, T.,Wang, R.,Wang, Z.,Wang, X.,Wang, F.,Ding, J.
Structural basis for Ragulator functioning as a scaffold in membrane-anchoring of Rag GTPases and mTORC1.
Nat Commun, 8:1394-1394, 2017

PubMed Abstract: Amino acid-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) is mediated by Rag GTPases, which are recruited to the lysosome by the Ragulator complex consisting of p18, MP1, p14, HBXIP and C7orf59; however, the molecular mechanism is elusive. Here, we report the crystal structure of Ragulator, in which p18 wraps around the MP1-p14 and C7orf59-HBXIP heterodimers and the interactions of p18 with MP1, C7orf59, and HBXIP are essential for the assembly of Ragulator. There are two binding sites for the Roadblock domains of Rag GTPases: helix α1 of p18 and the two helices side of MP1-p14. The interaction of Ragulator with Rag GTPases is required for their cellular co-localization and can be competitively inhibited by C17orf59. Collectively, our data indicate that Ragulator functions as a scaffold to recruit Rag GTPases to lysosomal membrane in mTORC1 signaling.

PubMed: 29123114
DOI: 10.1038/s41467-017-01567-4

Experimental method

X-RAY DIFFRACTION (2.9 Å)