Analysis of the results of the assays performed on the viable multiple alanine substitution mutants (summarized in Table 1 ) provoke the hypothesis that the L11 P-site loop may dynamically function to help the ribosome sense the occupancy status of the large ribosomal subunit P-site. This is modeled in Figure 6 . When the P-site is unoccupied, the P-site loop can extend into this space, moving away from the terminal loop of H84. Upon occupation of the P-site, the peptidyl-tRNA T-loop displaces the L11 P-site loop, causing its retraction into H84. By this model, the rRNA SHAPE analyses depicting increased protection of Helix 84 by the 51-4A mutant show that this mutant drives the L11 P-site loop equilibrium toward the 'retracted' state. Conversely, increased deprotection of Helix 84 in the 54-7A mutant suggests that this more mimics the P-site unoccupied state, i.e. the 'extended' P-site loop state. This analysis directly explains the P-site binding data. Retraction of the P-site loop from the P-site results in 51-4A ribosomes having higher intrinsic affinity for this substrate while extension of this structure into the P-site creates a steric clash with the peptidyl-tRNA T-loop, resulting in decreased affinity for this substrate. That neither mutant conferred optimal peptidyl-tRNA P-site occupancy may account for their hypersensitivity to sparsomycin, especially for 54-7A in which the P-site loop is already competing with the tRNA for the P-site. Mutants 57-60A, 51-60A and 51-60Á appear to disrupt the normal function of the P-site loop to a lethal level. In addition, the observation that tRNA binding to the P-site results in deprotection of C2675 implicates H84 itself as a structurally dynamic unit. The functional consequences of this are not clear, although it is tempting to speculate that this conformational change may play a role in the structural rearrangements of the B1b and B1c bridges between the pre-and post-translocational states.