5YK3

human Ragulator complex

Summary for 5YK3

• Entry DOI: 10.2210/pdb5yk3/pdb
• Descriptor: Ragulator complex protein LAMTOR3, Ragulator complex protein LAMTOR1, Ragulator complex protein LAMTOR4, ... (11 entities in total)
• Functional Keywords: cellular signal transduction, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 15
• Total formula weight: 169172.87

Authors

Wu, G.,Mu, Z. (deposition date: 2017-10-12, release date: 2019-01-23, Last modification date: 2024-03-27)

Primary citation

Mu, Z.,Wang, L.,Deng, W.,Wang, J.,Wu, G.
Structural insight into the Ragulator complex which anchors mTORC1 to the lysosomal membrane
Cell Discov, 3:17049-17049, 2017

PubMed Abstract: The mechanistic target of rapamycin (mTOR) signal-transduction pathway plays a key role in regulating many aspects of metabolic processes. The central player of the mTOR signaling pathway, mTOR complex 1 (mTORC1), is recruited by the pentameric Ragulator complex and the heterodimeric Rag GTPase complex to the lysosomal membrane and thereafter activated. Here, we determined the crystal structure of the human Ragulator complex, which shows that Lamtor1 possesses a belt-like shape and wraps the other four subunits around. Extensive hydrophobic interactions occur between Lamtor1 and the Lamtor2-Lamtor3, Lamtor4-Lamtor5 roadblock domain protein pairs, while there is no substantial contact between Lamtor2-Lamtor3 and Lamtor4-Lamtor5 subcomplexes. Interestingly, an α-helix from Lamtor1 occupies each of the positions on Lamtor4 and Lamtor5 equivalent to the α3-helices of Lamtor2 and Lamtor3, thus stabilizing Lamtor4 and Lamtor5. Structural comparison between Ragulator and the yeast Ego1-Ego2-Ego3 ternary complex (Ego-TC) reveals that Ego-TC only corresponds to half of the Ragulator complex. Coupling with the fact that in the Ego-TC structure, Ego2 and Ego3 are lone roadblock domain proteins without another roadblock domain protein pairing with them, we suggest that additional components of the yeast Ego complex might exist.

PubMed: 29285400
DOI: 10.1038/celldisc.2017.49

Experimental method

X-RAY DIFFRACTION (3.01 Å)