Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly

Jorge Cuéllar, W. Grant Ludlam, Nicole C. Tensmeyer, Takuma Aoba, Madhura Dhavale, César Santiago, M. Teresa Bueno-Carrasco, Michael J. Mann, Rebecca L. Plimpton, Aman Makaju, Sarah Franklin, Barry M. Willardson () and José M. Valpuesta ()
Additional contact information
Jorge Cuéllar: Campus de la Universidad Autónoma de Madrid
W. Grant Ludlam: Brigham Young University
Nicole C. Tensmeyer: Brigham Young University
Takuma Aoba: Brigham Young University
Madhura Dhavale: Brigham Young University
César Santiago: Campus de la Universidad Autónoma de Madrid
M. Teresa Bueno-Carrasco: Campus de la Universidad Autónoma de Madrid
Michael J. Mann: Brigham Young University
Rebecca L. Plimpton: Brigham Young University
Aman Makaju: University of Utah
Sarah Franklin: University of Utah
Barry M. Willardson: Brigham Young University
José M. Valpuesta: Campus de la Universidad Autónoma de Madrid

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract The mechanistic target of rapamycin (mTOR) kinase forms two multi-protein signaling complexes, mTORC1 and mTORC2, which are master regulators of cell growth, metabolism, survival and autophagy. Two of the subunits of these complexes are mLST8 and Raptor, β-propeller proteins that stabilize the mTOR kinase and recruit substrates, respectively. Here we report that the eukaryotic chaperonin CCT plays a key role in mTORC assembly and signaling by folding both mLST8 and Raptor. A high resolution (4.0 Å) cryo-EM structure of the human mLST8-CCT intermediate isolated directly from cells shows mLST8 in a near-native state bound to CCT deep within the folding chamber between the two CCT rings, and interacting mainly with the disordered N- and C-termini of specific CCT subunits of both rings. These findings describe a unique function of CCT in mTORC assembly and a distinct binding site in CCT for mLST8, far from those found for similar β-propeller proteins.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10781-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10781-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10781-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().