PMID- 29285400
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2056-5968 (Print)
IS  - 2056-5968 (Electronic)
IS  - 2056-5968 (Linking)
VI  - 3
DP  - 2017
TI  - Structural insight into the Ragulator complex which anchors mTORC1 to the 
      lysosomal membrane.
PG  - 17049
LID - 10.1038/celldisc.2017.49 [doi]
AB  - 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 alpha-helix from 
      Lamtor1 occupies each of the positions on Lamtor4 and Lamtor5 equivalent to the 
      alpha3-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.
FAU - Mu, Zongkai
AU  - Mu Z
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Wang, Lei
AU  - Wang L
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Deng, Wei
AU  - Deng W
AD  - National Center for Protein Science Shanghai, Shanghai, China.
FAU - Wang, Jiawei
AU  - Wang J
AD  - State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua 
      University, Beijing, China.
FAU - Wu, Geng
AU  - Wu G
AD  - State Key Laboratory of Microbial Metabolism, School of Life Sciences and 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20171226
PL  - England
TA  - Cell Discov
JT  - Cell discovery
JID - 101661034
PMC - PMC5742854
OTO - NOTNLM
OT  - Crystal structure
OT  - EGO-TC
OT  - Lamtor
OT  - Rag GTPase complex
OT  - Ragulator
OT  - mTORC1 signaling pathway
COIS- The authors declare no conflict of interest.
EDAT- 2017/12/30 06:00
MHDA- 2017/12/30 06:01
PMCR- 2017/12/26
CRDT- 2017/12/30 06:00
PHST- 2017/10/10 00:00 [received]
PHST- 2017/11/15 00:00 [accepted]
PHST- 2017/12/30 06:00 [entrez]
PHST- 2017/12/30 06:00 [pubmed]
PHST- 2017/12/30 06:01 [medline]
PHST- 2017/12/26 00:00 [pmc-release]
AID - celldisc201749 [pii]
AID - 10.1038/celldisc.2017.49 [doi]
PST - epublish
SO  - Cell Discov. 2017 Dec 26;3:17049. doi: 10.1038/celldisc.2017.49. eCollection 
      2017.