Fig. 7. A computational model for the SRP pathway emphasizes the role of NAC in maintaining targeting specificity.
a NC length dependence of SRP-SR association rate constants. All measurements used the same concentrations of RNC, SRP and NAC as in Fig. 2g. The red shaded area indicates NC lengths at which the signal sequence is partially or completely buried, assuming that the ribosome exit tunnel accommodates ~35 amino acids. The data were fit to Eq. (18) in the Methods section (solid lines) for RNC(ss) and to a constant kon value for RNC(ssmt). All experimental data are shown as mean ± SD, with n = 3–5 independent measurements on the same biological sample. b Computational model for co-translational protein targeting by SRP and SR. c, d Modeled progression curves for SRP-dependent protein targeting during ongoing protein synthesis with and without NAC present (c). The model in b was calculated as described in the Methods section, assuming that the signal sequence is located within the N-terminal 14 amino acids of the nascent protein and that the exit tunnel accommodates 35 amino acids. Values of kon,SR were from (a) (solid lines). The other parameters used for the modeling are summarized in d and detailed in the Methods section. e–k Sensitivity of the modeled targeting efficiency to perturbations of the individual parameters in the model. The fraction of successfully targeted RNCs at a nascent chain length of 150 aa was determined as in c, except that each of the parameters listed in d was varied by 1–2 orders of magnitude from the estimated values (dotted lines). Source data for a, c, and e–k are provided in the Source Data file.