FIGURE 7.

Intrinsic motions of tRNA within the PRE complex and their relationship to EF-G catalyzed translocation. (A) Spontaneous conformational changes in the PRE complex result in motions of A- and P-site tRNAs with respect to each other and the ribosome. Together with previous investigations (Munro et al. 2007; Agirrezabala et al. 2008; Julian et al. 2008), the present findings suggest the existence of an additional hybrid state intermediate, the H2* state, in which the 3′-CCA end of peptidyl-tRNA occupies the large subunit P site, while the peptidyl-tRNA body remains classically configured within the A site. (B) The present findings suggest that EF-G preferentially engages the A site of the PRE complex once it has spontaneously achieved a configuration in which (1) the unlocked state has been achieved (minimally including small subunit rotation, P/E hybrid state formation and L1 stalk closure [Munro et al. 2010a]) and (2) the H1 state has been achieved wherein the body of peptidyl-tRNA in the A site has moved toward the P site. (C) After productively engaging the A site, EF-G facilitates the process of translocation.