Tor forms a dimer through an N-terminal helical solenoid with a complex topology

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Cell Biology

Background:

• The target of rapamycin (Tor) is a crucial Ser/Thr protein kinase regulating cellular anabolic and catabolic processes.
• Tor exists in two complexes, TORC1 and TORC2, sharing a common Tor-Lst8 heterodimer sub-complex.

Purpose of the Study:

• To determine the cryo-electron microscopy (EM) structure of the Tor-Lst8 complex.
• To elucidate the assembly and structural organization of Tor complexes.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine the structure of Tor bound to Lst8.
• Structural analysis of the Tor-Lst8 heterodimer and its assembly into higher-order structures.

Main Results:

• The cryo-EM structure of Tor bound to Lst8 was determined.
• Two Tor-Lst8 heterodimers form a dyad-symmetry dimer via Tor-Tor interactions.
• The N-terminal 1,300 residues of Tor form a HEAT repeat-containing α-solenoid with distinct segments (spiral, bridge, railing, cap).
• A novel structural interpretation of mTORC1 is proposed, where the Tor spiral interacts with the Tor bridge, forming a platform for RAPTOR.

Conclusions:

• The determined structure provides a new framework for understanding Tor complex assembly and regulation.
• This structural insight is critical for deciphering the mechanisms of mTORC1 signaling.
• The findings offer a re-interpretation of the mTORC1 structure and its functional implications.