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Sub-cellular biochemistry
2024;104 459-483.

Maturation and Assembly of mTOR Complexes by the HSP90-R2TP-TTT Chaperone System: Molecular Insights and Mechanisms.

Andr��s L��pez-Perrote, Marina Serna, Oscar Llorca
Author Information
  1. Andr��s L��pez-Perrote: Spanish National Cancer Research Centre (CNIO), Structural Biology Programme, Melchor Fern��ndez Almagro 3, Madrid, Spain. aperrote@cnio.es.
  2. Marina Serna: Spanish National Cancer Research Centre (CNIO), Structural Biology Programme, Melchor Fern��ndez Almagro 3, Madrid, Spain.
  3. Oscar Llorca: Spanish National Cancer Research Centre (CNIO), Structural Biology Programme, Melchor Fern��ndez Almagro 3, Madrid, Spain. ollorca@cnio.es.
PMID: 38963496 DOI: 10.1007/978-3-031-58843-3_17

Abstract

The mechanistic target of rapamycin (mTOR) is a master regulator of cell growth and metabolism, integrating environmental signals to regulate anabolic and catabolic processes, regulating lipid synthesis, growth factor-induced cell proliferation, cell survival, and migration. These activities are performed as part of two distinct complexes, mTORC1 and mTORC2, each with specific roles. mTORC1 and mTORC2 are elaborated dimeric structures formed by the interaction of mTOR with specific partners. mTOR functions only as part of these large complexes, but their assembly and activation require a dedicated and sophisticated chaperone system. mTOR folding and assembly are temporarily separated with the TELO2-TTI1-TTI2 (TTT) complex assisting the cotranslational folding of mTOR into a native conformation. Matured mTOR is then transferred to the R2TP complex for assembly of active mTORC1 and mTORC2 complexes. R2TP works in concert with the HSP90 chaperone to promote the incorporation of additional subunits to mTOR and dimerization. This review summarizes our current knowledge on how the HSP90-R2TP-TTT chaperone system facilitates the maturation and assembly of active mTORC1 and mTORC2 complexes, discussing interactions, structures, and mechanisms.

Keywords

Chaperones HSP90 R2TP RUVBL1 RUVBL2 TELO2 TTT mTORC1 mTORC2

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MeSH Term

Humans
HSP90 Heat-Shock Proteins
Molecular Chaperones
Animals
TOR Serine-Threonine Kinases
Mechanistic Target of Rapamycin Complex 2
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes
Signal Transduction

Chemicals

HSP90 Heat-Shock Proteins
Molecular Chaperones
TOR Serine-Threonine Kinases
Mechanistic Target of Rapamycin Complex 2
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes
MTOR protein, human
Journal Article Review

Word Cloud

Created with Highcharts 10.0.0mTORmTORC1mTORC2complexesassemblycellchaperoneR2TPgrowthpartspecificstructuressystemfoldingTTTcomplexactiveHSP90HSP90-R2TP-TTTmechanistictargetrapamycinmasterregulatormetabolismintegratingenvironmentalsignalsregulateanaboliccatabolicprocessesregulatinglipidsynthesisfactor-inducedproliferationsurvivalmigrationactivitiesperformedtwodistinctroleselaborateddimericformedinteractionpartnersfunctionslargeactivationrequirededicatedsophisticatedtemporarilyseparatedTELO2-TTI1-TTI2assistingcotranslationalnativeconformationMaturedtransferredworksconcertpromoteincorporationadditionalsubunitsdimerizationreviewsummarizescurrentknowledgefacilitatesmaturationdiscussinginteractionsmechanismsMaturationAssemblyComplexesChaperoneSystem:MolecularInsightsMechanismsChaperonesRUVBL1RUVBL2TELO2

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