Fig. 7. Schematic model for the functional cycle of MtbEttA in the course of ATP hydrolysis.

The monomer formation involves dissociation of the domain-swapped dimer (the favored configuration in solution) and rearrangement of the two NBDs to form a compact but open conformation. The monomeric MtbEttA transits to the closed conformation after binding to the E-site of the 70SIC in the presence of ATP molecules. At the pre-hydrolysis stage, the engagement of the Q-loop at NBS-II requires conformational change of the H-switch and A-loop in NBS-I, which is mediated by the bending of PtIM α1 along with the 30S rotation. In addition, the tip of PtIM and the CCA tail of tRNA become distorted. Meanwhile, remodeling of the 50S occurs as a result of the occupancy of MtbEttA at the E-site and the intermediate rotation of 30S. In the transition state, MtbEttA and the P-site tRNA maintain stable interactions due to a more restricted 30S movement. The head swiveling and body rotation of 30S are indicated with arrows for the movement in the previous (gray arrows) and current (black arrows) steps, respectively, in a sequence of nonrotated, Pre_R0, Pre_R1, Trans_R1, and Trans_R0 states. At the post-hydrolysis stage, MtbEttA adopts an open conformation and disassociates from the ribosome. ADP dissociation and ATP reloading are necessary for the next cycle.