Signal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation

Proteins destined for the secretory compartment of the cell are cotranslationally translocated into the endoplasmic reticulum. The majority of these proteins are N-glycosylated, a co- and posttranslational modification that ensures proper protein folding, stability, solubility, and cellular localization. Here, we show that the beta subunit of the signal recognition particle receptor (SR) is required for assembly of the N-glycosylation-competent translocon. We report that guanine analog chemical probes identified by high-throughput screening or mutation of the SR-beta guanosine triphosphate binding site cause an N-glycosylation-deficient phenotype. Neither method alters the association of SR-alpha with SR-beta, but both approaches reduce the association of SR-beta with the oligosac-charyltransferase complex. These experiments demonstrate that SR-beta has a previously unrecognized function coordinating endoplasmic reticulum translation with N-glycosylation.