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

Autor:	Cuéllar J; Centro Nacional de Biotecnología, Campus de la Universidad Autónoma de Madrid, 28049, Madrid, Spain., Ludlam WG; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA., Tensmeyer NC; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA., Aoba T; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA., Dhavale M; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA., Santiago C; Centro Nacional de Biotecnología, Campus de la Universidad Autónoma de Madrid, 28049, Madrid, Spain., Bueno-Carrasco MT; Centro Nacional de Biotecnología, Campus de la Universidad Autónoma de Madrid, 28049, Madrid, Spain., Mann MJ; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA., Plimpton RL; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA., Makaju A; Department of Internal Medicine, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA., Franklin S; Department of Internal Medicine, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA., Willardson BM; Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA. bmwillardson@chem.byu.edu., Valpuesta JM; Centro Nacional de Biotecnología, Campus de la Universidad Autónoma de Madrid, 28049, Madrid, Spain. jmv@cnb.csic.es.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2019 Jun 28; Vol. 10 (1), pp. 2865. Date of Electronic Publication: 2019 Jun 28.
DOI:	10.1038/s41467-019-10781-1
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu