Cryo-EM shows TOR dimerizes through an N-terminal helical solenoid, informing mTORC1 architecture.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Cryo-EM structure |
| Journal | Nature communications |
| Year | 2016 |
| Peer reviewed | Yes |
| Source | DOI 10.1038/ncomms11016 · PMID 27072897 · Free full text (PMC4833857) |
The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a range of anabolic and catabolic processes. Tor is present in two complexes, TORC1 and TORC2, in which the Tor-Lst8 heterodimer forms a common sub-complex. We have determined the cryo-electron microscopy (EM) structure of Tor bound to Lst8. Two Tor-Lst8 heterodimers assemble further into a dyad-symmetry dimer mediated by Tor-Tor interactions. The first 1,300 residues of Tor form a HEAT repeat-containing alpha-solenoid with four distinct segments: a highly curved 800-residue N-terminal 'spiral', followed by a 400-residue low-curvature 'bridge' and an extended 'railing' running along the bridge leading to the 'cap' that links to FAT region. This complex topology was verified by domain insertions and offers a new interpretation of the mTORC1 structure. The spiral of one TOR interacts with the bridge of another, which together form a joint platform for the Regulatory Associated Protein of TOR (RAPTOR) regulatory subunit.
| Intervention | Structural (cryo-EM) |
| Target | TOR / Lst8 |
| Model | Cryo-EM structure |
| Effect | Tor-Lst8 heterodimers assemble into a dyad-symmetric dimer via Tor-Tor interactions (N-terminal solenoid) |