Fig. 3: Ensemble of C-terminal interactions promote gate opening in the h20S.
From: The YΦ motif defines the structure-activity relationships of human 20S proteasome activators
a Opt5 sequence in the h20S α-pockets. The α-subunits are numbered according to the yeast proteasome. Center, a top-view 3D density map of the liganded α-ring displaying color-coded densities for each C-tail. The empty α-pocket (α7/α1) is marked by a red dotted circle. Close-up views of each C-terminal Opt5 sequence (stick) is superimposed over their corresponding cryo-EM densities (mesh). PA26E102A-Opt5 induces terminus-dependent conformational changes throughout the inner (purple) and outer (gray) regions of the α-pockets relative to the apo h20S (outlined) (PDB ID: 4R3O). Predicted interactions (pink coils) and unobserved canonical interactions (black dotted circles) are denoted. Anchored (A) or unanchored (U) Opt5 binding states are labeled at the bottom-left corner of each panel (see text). b Summary table of the interactions for each α-pocket. c Opt5 binds with distinct conformations in the A and U states. Opt5 forms an α-helix In the U state (α1/α2-pocket), while it adopts a β-strand conformation in the A state. Overlaying the C-tails highlights the distinct backbone conformations between the A and U states, while also showing the striking similarities between the A states, especially in the position of the P2 and P3 Tyr side chains. See Supplementary Table 2 for relative densities of the C-tails (b) and torsion angles (c).
