Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling

Mariana E.G. De Araujo, Andreas Naschberger, Barbara G. Fürnrohr, Taras Stasyk, Theresia Dunzendorfer-Matt, Stefan Lechner, Stefan Welti, Leopold Kremser, Giridhar Shivalingaiah, Martin Offterdinger, Herbert H. Lindner, Lukas A. Huber, Klaus Scheffzek

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The LAMTOR [late endosomal and lysosomal adaptor and MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) activator] complex, also known as "Ragulator," controls the activity of mTOR complex 1 (mTORC1) on the lysosome.The crystal structure of LAMTOR consists of two roadblock/LC7 domain-folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag guanosine triphosphatases (GTPases) associated with the pentamer through their carboxyl-terminal domains, predefining the orientation for interaction with mTORC1. In vitro reconstitution and experiments with site-directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling. Functional data validated the effect of two short LAMTOR1 amino acid regions in recruitment and stabilization of the Rag GTPases.
Original languageEnglish (US)
Pages (from-to)377-381
Number of pages5
JournalScience
Volume358
Issue number6361
DOIs
StatePublished - Oct 20 2017
Externally publishedYes

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Generated from Scopus record by KAUST IRTS on 2023-02-15

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