6QB8

Human CCT:mLST8 complex

Summary for 6QB8

• Entry DOI: 10.2210/pdb6qb8/pdb
• EMDB information: 4489
• Descriptor: T-complex protein 1 subunit alpha, T-complex protein 1 subunit beta, T-complex protein 1 subunit delta, ... (9 entities in total)
• Functional Keywords: cct, folding, wd40, mlst8, chaperone
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 16
• Total formula weight: 947765.17

Authors

Cuellar, J.,Santiago, C.,Ludlam, W.G.,Bueno-Carrasco, M.T.,Valpuesta, J.M.,Willardson, B.M. (deposition date: 2018-12-20, release date: 2019-07-03, Last modification date: 2024-10-09)

Primary citation

Cuellar, J.,Ludlam, W.G.,Tensmeyer, N.C.,Aoba, T.,Dhavale, M.,Santiago, C.,Bueno-Carrasco, M.T.,Mann, M.J.,Plimpton, R.L.,Makaju, A.,Franklin, S.,Willardson, B.M.,Valpuesta, J.M.
Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly.
Nat Commun, 10:2865-2865, 2019

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 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.

PubMed: 31253771
DOI: 10.1038/s41467-019-10781-1

Experimental method

ELECTRON MICROSCOPY (3.97 Å)