5x6u
From Proteopedia
Crystal structure of human heteropentameric complex
Structural highlights
FunctionLTOR3_HUMAN As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.[1] [2] Publication Abstract from PubMedThe 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. Structural basis for the assembly of the Ragulator-Rag GTPase complex.,Yonehara R, Nada S, Nakai T, Nakai M, Kitamura A, Ogawa A, Nakatsumi H, Nakayama KI, Li S, Standley DM, Yamashita E, Nakagawa A, Okada M Nat Commun. 2017 Nov 20;8(1):1625. doi: 10.1038/s41467-017-01762-3. PMID:29158492[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Kitamura A | Li S | Nada S | Nakagawa A | Nakai M | Nakai T | Nakatsumi H | Nakayama KI | Ogawa A | Okada M | Standley DM | Yamashita E | Yonehara R
