SecYEG drives conformational changes in the RNC–SRP–FtsY complex. (A) Free energy profile for the FtsY–SRP interaction in the absence (black) and presence (red) of SecYEG. The red arrows denote the effect of SecYEG. Activation energies were calculated from the rate constants using ΔG^‡ = –RTln[kh/(k_BT)], where R = 1.987 cal·K⁻¹·mol⁻¹, h = 1.58 × 10⁻³⁷ kcal−s, k_B = 3.3 × 10⁻²⁷ kcal·K⁻¹, and T = 298 K. The relative free energies were calculated from the equilibrium stability of the complexes using ΔG = –RTlnK, where K is the equilibrium constant. A standard state of 1 µM was used. T denotes GTP and D denotes GDP. (B) Model for the role of SecYEG in driving GTPase rearrangements in the targeting complex and completing cotranslational protein targeting. The M domain of Ffh is also shown. The question mark denotes questions regarding the fate of the signal sequence and the interaction of SecYEG with FtsY in the quaternary complex.