Leucine-sensing mechanism of leucyl-tRNA synthetase 1 for mTORC1 activation.
X-ray crystallography
conformational change
leucine sensing
leucyl-tRNA synthetase 1
mechanistic target of rapamycin complex 1
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
27 04 2021
27 04 2021
Historique:
received:
05
07
2020
revised:
18
12
2020
accepted:
02
04
2021
entrez:
28
4
2021
pubmed:
29
4
2021
medline:
9
2
2022
Statut:
ppublish
Résumé
Leucyl-tRNA synthetase 1 (LARS1) mediates activation of leucine-dependent mechanistic target of rapamycin complex 1 (mTORC1) as well as ligation of leucine to its cognate tRNAs, yet its mechanism of leucine sensing is poorly understood. Here we describe leucine binding-induced conformational changes of LARS1. We determine different crystal structures of LARS1 complexed with leucine, ATP, and a reaction intermediate analog, leucyl-sulfamoyl-adenylate (Leu-AMS), and find two distinct functional states of LARS1 for mTORC1 activation. Upon leucine binding to the synthetic site, H251 and R517 in the connective polypeptide and
Identifiants
pubmed: 33910001
pii: S2211-1247(21)00345-4
doi: 10.1016/j.celrep.2021.109031
pii:
doi:
Substances chimiques
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Leucine-tRNA Ligase
EC 6.1.1.4
Leucine
GMW67QNF9C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109031Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.