Extended Data Fig. 8: Geometries of nucleotide-binding pockets and nucleotide-driven intrasubunit conformational changes of AAA domains.
From: Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome
a, Comparison of the nucleotide-binding pockets of six ATPases in all states illustrates a common pattern in the geometry of the nucleotide-binding sites. Each row shows the geometry of the nucleotide-binding pocket of one ATPase in all six states. In each panel showing an ATP or ADP-bound state, one red dashed line marks the distance from the β- or γ-phosphate of the nucleotide to the arginine finger of the adjacent ATPase, and the other line marks the distance from the same phosphate to the Walker B motif. In the case of apo-like states, the red lines extend to the proline of the Walker A motif rather than to the phosphate groups. These geometries indicate the potential reactivity of these sites33. When the ATPase is positioned in the middle of the pore-loop staircase, but not at the lowest position, the nucleotide-binding pockets are tightly packed regardless of whether ATP or ADP is bound. By contrast, when the ATPase is either in the lowest position of the substrate-pore loop staircase or disengaged from the substrate, the nucleotide-binding pocket is rather open regardless of whether it is ADP-bound or free of nucleotide. b–e, Superpositions of the AAA domain structures of RPT1 (b), RPT2 (c), RPT3 (d) or RPT4 (e) from six distinct states aligned against their large AAA subdomains. RPT1 assumes two major conformations and RPT2 assumes three.
