Extended Data Fig. 6: Electrostatic surface, conservation, and binding of inositol hexakisphosphate (InsP6) to TRRAP.

a. Electrostatic surface representation of hSAGA shown from three different views. Only regions with all-atom models have been included. Regions of lower sequence assignment confidence (unknown, UNKs) were excluded from the calculation and are shown as white cartoon. A highly positive charged tunnel between the FAT, HEAT, and ΨPIKK domains of TRRAP and SUPT20H is indicated. b. Close-up view of the InsP₆ binding pocket within this tunnel. c. Same views as in a colored by sequence conservation (white cartoon as in a). d. Close-up view of the InsP₆ binding pocket. InsP₆ (shown in stick representation) is bound by a half-ring of highly conserved residues. e. Close-up view of the atomic model and the LocSpiral filtered multibody map (contoured at 11 σ) of TRRAP. The view corresponds to a back view of Fig. 3f (rotated 180°). Residues involved in InsP₆ binding are indicated. All labeled residues are part of the TRRAP FAT domain except for K3547 (within ΨPIKK). Atoms are colored by conservation (carbon, see panel d), pink (carbon of InsP₆), red (oxygen), blue (nitrogen), or orange (phosphorus). f. View as indicated by boxes in a and c (colored by domains and subunits). g, h. Comparison of InsP₆ binding in hSAGA and in human mTORC2³¹ shown in cartoon representation. In both complexes InsP₆ binds in a similar location between the FAT and pseudo- and kinase domains of hSAGA and mTORC2, respectively. i. In the ySAGA complex structures (here PDB: 6T9J) the central part of the FAT domain is poorly resolved (red circle) and presumably flexible (translucent map contoured at 11 σ). This region contains residues (red arrow) involved in InsP₆ binding in hSAGA (for example R3051 and K3055, see panel e). j. Unattributed density (red circle) in the earlier determined structure of isolated Tra1 (PDB: 5OJS, translucent map contoured at 7.5 σ).