Fig. 8. Model for how NAC allosterically regulates SRP to ensure the specificity of cotranslational protein targeting.
Left panel: Without NAC, the ribosome dominates the interactions of SRP, and even RNCs with a weak signal sequence (red zigzag line) or with a short nascent chain can induce SRP to dynamically sample the proximal conformation that rapidly associates with SR at the ER. Right panel: NAC (purple) co-binds with SRP to a variety of RNCs and selectively drives SRPs into inactive conformations on RNCs with a weak signal sequence or a short nascent chain, thus inhibiting the ER localization of ribosomes without an exposed and functional signal sequence.