An interaction between the SRP receptor and the translocon is critical during cotranslational protein translocation

T he signal recognition particle (SRP)-dependent targeting pathway facilitates rapid, efficient delivery of the ribosome-nascent chain complex (RNC) to the protein translocation channel. We test whether the SRP receptor (SR) locates a vacant protein translocation channel by interacting with the yeast Sec61 and Ssh1 translocons. Surprisingly, the slow growth and cotranslational translocation defects caused by deletion of the transmembrane (TM) span of yeast SR beta (SR beta-Delta TM) are exaggerated when the SSH1 gene is disrupted. Disruption of the SBH2 gene, which encodes the Beta subunit of the Ssh1p complex, likewise causes a growth defect when combined with SR beta-Delta TM. Cotranslational translocation defects in the ssh1 Delta SR beta-Delta TM mutant are explained by slow and inefficient in vivo gating of translocons by RNCs. A critical function for translocation channel beta subunits in the SR-channel interaction is supported by the observation that simultaneous deletion of Sbh1p and Sbh2p causes a defect in the cotranslational targeting pathway that is similar to the translocation defect caused by deletion of either subunit of the SR.