Extended Data Fig. 8: Structural comparison of the PIKK FAT domains.
From: InsP6 binding to PIKK kinases revealed by the cryo-EM structure of an SMG1–SMG8–SMG9 complex
Structural comparison of the FAT domains of SMG1 with that of the other PIKK family members. In this figure, all structures are shown in the same orientation after optimal manual superposition of their FAT domains (FAT in violet, catalytic domain in slate, N-terminal HEAT in yellow). (a) mTOR (mammalian target of rapamycin) is from the PDB, code 4JSV, ATM (ataxia telangiectasia-mutated) is from the PDB, code 5MP0, ATR (ataxia- and Rad3-related) is from the PDB, code 5X60, DNA-PK (DNA protein kinase) is from the PDB, code 5LUQ, and the related protein TRRAP (transformation/transcription domain-associated protein) is from the PDB, code 5OJS. (b) Superposition of the structures shown in (a), despite poor structural conservation of the position and orientation of individual helices, the overall cleft-like feature that in SMG1 binds IP6 appears to be conserved within the PIKK family. Comparing the contact potential of each protein (not shown) we observe that the surface of this cleft is distinctly positive in SMG1, mTOR, TRRAP and ATR. The contact potential of DNA-PK is not as positive, and ATM was not included in this comparison due to the low resolution of this region.
