Extended Data Fig. 5: G-fold protein regulators of SMG1 and mTOR.
From: InsP6 binding to PIKK kinases revealed by the cryo-EM structure of an SMG1–SMG8–SMG9 complex
G-fold protein regulators of the cytoplasmic PIKK proteins, SMG1 and mTOR. Structures of SMG1 bound to the G-domain proteins, SMG8 and SMG9 (a), and of mTOR bound to RHEB (PDB, code 6BCU) (b) are shown in similar orientations after superimposition of the kinase domains of SMG1 and mTOR. Although the overall binding site is similar, there are major differences. First, RHEB is a bona fide GTPase, whereas the G-domain regulators of SMG1 binds ATP rather than GTP, and may well lack catalytic activity. Second, RHEB is positioned with its GTP domain roughly facing the catalytic cleft of mTOR, in an opposite orientation to that of SMG9. Unlike SMG9, RHEB binds to HEAT repeats proximal to the catalytic head (‘bridge’), as well as the very N-terminal HEAT repeats of mTOR (‘horn’). Significantly, the ‘bridge’ region of the mTOR HEAT repeats forms an extensive interface with the globular RHEB and largely replaces the equivalent position of SMG8 in the SMG1 structure.
