PMID- 30503338
OWN - NLM
STAT- MEDLINE
DCOM- 20190603
LR  - 20191210
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 508
IP  - 2
DP  - 2019 Jan 8
TI  - Crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free 
      states.
PG  - 387-391
LID - S0006-291X(18)32579-8 [pii]
LID - 10.1016/j.bbrc.2018.11.147 [doi]
AB  - The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a master 
      regulator of metabolism and cell growth. Among the numerous extracellular and 
      intracellular signals, certain amino acids activate mTORC1 in a Rag-dependent 
      manner. Arginine can stimulate mTORC1 activity by releasing the inhibitor CASTOR1 
      (Cellular Arginine Sensor of mTORC1) from GATOR2, a positive regulator of mTORC1 
      which interacts with GATOR1, the GAP for RagA/B. Three groups have resolved the 
      structures of arginine-CASTOR1 complex, shedding a new light on molecular basis 
      of the regulation of mTORC1 activity by arginine. However, lacking the apo 
      structure of CASTOR1 prelimited the molecular understanding of mechanism 
      underlying mTORC1 regulation. Here, we report crystal structures of arginine 
      sensor CASTOR1 in arginine-bound and ligand free states at 2.05 A and 2.8 A, 
      respectively. Structural comparison of CASTOR1 between two states reveals near 
      identical conformations, except in two loop regions. It indicates CASTOR1 does 
      not undergo large conformational change during arginine binding. Therefore, we 
      conclude a detailed structural interpretation of arginine sensing by CASTOR1 in 
      mTORC1 pathway.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Zhou, Yanxia
AU  - Zhou Y
AD  - State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 
      Chengdu, 610041, China.
FAU - Wang, Chen
AU  - Wang C
AD  - State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 
      Chengdu, 610041, China.
FAU - Xiao, Qingjie
AU  - Xiao Q
AD  - State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 
      Chengdu, 610041, China.
FAU - Guo, Li
AU  - Guo L
AD  - State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 
      Chengdu, 610041, China. Electronic address: guol325@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181128
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CASTOR1 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Recombinant Proteins)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Animals
MH  - Arginine/*metabolism
MH  - Binding Sites
MH  - Carrier Proteins/*chemistry/genetics/*metabolism
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ligands
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Models, Molecular
MH  - Protein Conformation
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Sf9 Cells
MH  - Signal Transduction
MH  - Spodoptera
MH  - Static Electricity
OTO - NOTNLM
OT  - CASTOR1
OT  - Structural analysis
OT  - arginine
OT  - mTORC1
EDAT- 2018/12/07 06:00
MHDA- 2019/06/04 06:00
CRDT- 2018/12/04 06:00
PHST- 2018/11/09 00:00 [received]
PHST- 2018/11/21 00:00 [accepted]
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2019/06/04 06:00 [medline]
PHST- 2018/12/04 06:00 [entrez]
AID - S0006-291X(18)32579-8 [pii]
AID - 10.1016/j.bbrc.2018.11.147 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Jan 8;508(2):387-391. doi: 
      10.1016/j.bbrc.2018.11.147. Epub 2018 Nov 28.