5X6V

Crystal structure of human heteroheptameric complex

Summary for 5X6V

• Entry DOI: 10.2210/pdb5x6v/pdb
• Related: 5X6U
• Descriptor: Ragulator complex protein LAMTOR3, Ragulator complex protein LAMTOR2, Ragulator complex protein LAMTOR5, ... (10 entities in total)
• Functional Keywords: ragulator rag gtpase complex, scaffold, roadblock, lysosome, mtor signaling, cell growth, protein binding
• Biological source: Homo sapiens (Human); More
• Cellular location: Late endosome membrane ; Peripheral membrane protein ; Cytoplasmic side : Q9UHA4 Q9Y2Q5; Cytoplasm: O43504 Q7L523 Q99K70; Lysosome : Q0VGL1; Late endosome membrane; Lipid-anchor; Cytoplasmic side: Q6IAA8
• Total number of polymer chains: 7
• Total formula weight: 92674.85

Authors

Yonehara, R.,Nada, S.,Nakai, T.,Nakai, M.,Kitamura, A.,Ogawa, A.,Nakatsumi, H.,Nakayama, K.I.,Li, S.,Standley, D.M.,Yamashita, E.,Nakagawa, A.,Okada, M. (deposition date: 2017-02-23, release date: 2017-12-06, Last modification date: 2023-11-22)

Primary citation

Yonehara, R.,Nada, S.,Nakai, T.,Nakai, M.,Kitamura, A.,Ogawa, A.,Nakatsumi, H.,Nakayama, K.I.,Li, S.,Standley, D.M.,Yamashita, E.,Nakagawa, A.,Okada, M.
Structural basis for the assembly of the Ragulator-Rag GTPase complex.
Nat Commun, 8:1625-1625, 2017

PubMed Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) plays a central role in regulating cell growth and metabolism by responding to cellular nutrient conditions. The activity of mTORC1 is controlled by Rag GTPases, which are anchored to lysosomes via Ragulator, a pentameric protein complex consisting of membrane-anchored p18/LAMTOR1 and two roadblock heterodimers. Here we report the crystal structure of Ragulator in complex with the roadblock domains of RagA-C, which helps to elucidate the molecular basis for the regulation of Rag GTPases. In the structure, p18 wraps around the three pairs of roadblock heterodimers to tandemly assemble them onto lysosomes. Cellular and in vitro analyses further demonstrate that p18 is required for Ragulator-Rag GTPase assembly and amino acid-dependent activation of mTORC1. These results establish p18 as a critical organizing scaffold for the Ragulator-Rag GTPase complex, which may provide a platform for nutrient sensing on lysosomes.

PubMed: 29158492
DOI: 10.1038/s41467-017-01762-3

Experimental method

X-RAY DIFFRACTION (2.02 Å)