[New structures of mTORC1: Focus on Rag GTPases].
Une moisson de nouvelles structures de mTORC1 - Coup de projecteur sur les GTPases Rag.
Cell Proliferation
Cryoelectron Microscopy
GTP Phosphohydrolases
/ chemistry
Guanosine Diphosphate
/ metabolism
Guanosine Triphosphate
/ metabolism
Humans
Lysosomes
Mechanistic Target of Rapamycin Complex 1
/ chemistry
Monomeric GTP-Binding Proteins
/ chemistry
Protein Structure, Quaternary
Proto-Oncogene Proteins
/ chemistry
Ras Homolog Enriched in Brain Protein
/ chemistry
Regulatory-Associated Protein of mTOR
/ chemistry
TOR Serine-Threonine Kinases
/ chemistry
Tumor Suppressor Proteins
/ chemistry
Journal
Medecine sciences : M/S
ISSN: 1958-5381
Titre abrégé: Med Sci (Paris)
Pays: France
ID NLM: 8710980
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
entrez:
28
4
2021
pubmed:
29
4
2021
medline:
9
11
2021
Statut:
ppublish
Résumé
mTORC1 is a central player in cell growth, a process that is tightly regulated by the availability of nutrients and that controls various aspects of metabolism in the normal cell and in severe diseases such as cancers. mTORC1 is a large multiprotein complex, composed of the kinase subunit mTOR, of Ragulator, which attaches mTOR to the lysosome membrane, of the atypical Rag GTPases and the small GTPase RheB, whose nucleotide states directly dictate its localization to the lysosome and its kinase activity, and of RAPTOR, an adaptor that assembles the complex. The activity of the Rag GTPases is further controlled by the GATOR1 and folliculin complexes, which regulate their GTP/GDP conversion. Here, we review recent structures of important components of the mTORC1 machinery, determined by cryo-electron microscopy for the most part, which allow to reconstitute the architecture of active mTORC1 at near atomic resolution. Notably, we discuss how these structures shed new light on the roles of Rag GTPases and their regulators in mTORC1 regulation, and the perspectives that they open towards understanding the inner workings of mTORC1 on the lysosomal membrane. Une moisson de nouvelles structures de mTORC1 - Coup de projecteur sur les GTPases Rag. mTORC1 est un acteur central de la croissance cellulaire, un processus étroitement régulé par la disponibilité de nutriments et qui contrôle diverses étapes du métabolisme dans la cellule normale et au cours de maladies, comme les cancers. mTORC1 est un complexe multiprotéique de grande taille constitué de nombreuses sous-unités, parmi lesquelles deux types de GTPases, Rag et RheB, contrôlent directement sa localisation membranaire et son activité kinase. Dans cette revue, nous faisons le point sur une moisson de structures récentes, déterminées pour la plupart par cryo-microscopie électronique, qui sont en passe de reconstituer le puzzle de l’architecture de mTORC1. Nous discutons ce que ces structures révèlent sur le rôle des GTPases, et ce que leur connaissance ouvre comme perspectives pour comprendre comment mTORC1 fonctionne à la membrane du lysosome.
Autres résumés
Type: Publisher
(fre)
Une moisson de nouvelles structures de mTORC1 - Coup de projecteur sur les GTPases Rag.
Identifiants
pubmed: 33908855
doi: 10.1051/medsci/2021033
pii: msc200371
doi:
Substances chimiques
FLCN protein, human
0
Proto-Oncogene Proteins
0
Ras Homolog Enriched in Brain Protein
0
Regulatory-Associated Protein of mTOR
0
Tumor Suppressor Proteins
0
Guanosine Diphosphate
146-91-8
Guanosine Triphosphate
86-01-1
MTOR protein, human
EC 2.7.1.1
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
GTP Phosphohydrolases
EC 3.6.1.-
Monomeric GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Review
Langues
fre
Sous-ensembles de citation
IM
Pagination
372-378Informations de copyright
© 2021 médecine/sciences – Inserm.
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