Activated GTPase Movement on SRP RNA Drives Cotranslational Protein Targeting

Signal Recognition Particle (SRP) and its receptor (SR) are co-translational protein targeting machineries responsible for delivering ribosome-nascent chain-complexes (RNCs) from cytosol to cellular membranes. Loaded with its cargo (RNC), SRP forms a complex with SR and bring the RNC to the membrane. Extensive rearrangements in this complex activate GTP hydrolysis and unload the RNC onto the translocon. During this process, the SRP RNA plays an essential role in accelerating both SRP-SR complex formation and GTP hydrolysis step. Here we show that the SRP RNA is a bi-functional molecule with its two ends, the tetraloop end and the distal end, stimulating different stages of SRP-SR interaction. using single molecule techniques to direct visualize the global relocalization along the SRP RNA, we demonstrate that the SRP-SR GTPase complex travels over 100A in the targeting reaction, from the RNA's tetraloop end during initial complex assembly to the distal end during GTPase activation. Moreover, this rearrangement is tightly regulated by the RNC and the translocon. The large-scale movement of the GTPase complex provides an attractive mechanism for coupling GTPase activation to the transfer of RNC from SRP to translocon, thereby ensuring productive protein targeting