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Title | Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly. |
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Journal, issue, pages | Nat Commun, Vol. 10, Issue 1, Page 2865, Year 2019 |
Publish date | Jun 28, 2019 |
Authors | 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 / José M Valpuesta / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:31253771 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.97 - 7.5 Å |
Structure data | EMDB-4503: |
Chemicals | ChemComp-ADP: |
Source |
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Keywords | CHAPERONE / CCT / folding / WD40 / mLST8 |