Fig. 8.

Model of SHLD2.3–REV7 dimer complex remodeling mediated by the ATP-driven translocation of the TRIP13 hexamer. (A and B)Schematic of the proposed remodeling mechanism of TRIP13-mediated SHLD2.3–REV7 dimer. The fingers of TRIP13 grip the REV7^NT threaded segment tightly and the translocation of TRIP13 monomers draws the thread from REV7 into the channel in stepwise manner. (Cand D) Models of the SHLD2.3–REV7₄–TRIP13 complexes in basal state 0 and basal state 1 (before and after the first catalytic cycle, see more details in Movie S1). For clarity, only one copy of SHLD2.3–REV7 dimer is shown in a sphere representation. In basal state 0 (C), TRIP13 monomers A₀, B₀, and C₀ hold the C-REV7^NT, while monomer E₀ contacts O-REV7. As shown in D, the first cycle of ATP hydrolysis occurs in monomer E₀, which transforms from a compact ATP-bound state to the flexible apo-state E₁; the neighboring seam monomer F₀ binds one ATP molecule to adopt the ATP-bound F₁ state. These structural changes cause F₁ to climb to the top of the AAA⁺ spiral to push an anticlockwise rotation of the SHLD2.3–REV7 dimer, which renders O-REV7 to form new contacts with monomer D₁.