Unregulated exposure of the ribosomal M-site caused by NAC depletion results in delivery of non-secretory polypeptides to the Sec61 complex

Nascent polypeptide associated complex (NAC) interacts with nascent polypep tides emerging from ribosomes, Both signal recognition particle (SRP) and N AC work together to ensure specificity in co-translational targeting by com peting for binding to the ribosomal membrane attachment site. While SRP sel ects signal-containing ribosomes for targeting, NAC prevents targeting of s ignal peptide-less nascent chains to the endoplasmic reticulum membrane. He re we show that the ribosome binding that occurs in NAC's absence delivers signalless nascent chains to the Sec61 complex, underscoring the danger of unregulated exposure of the ribosomal M-site, Recently, the idea that NAC p revents ribosome binding has been challenged. By carefully examining the ph ysiologic NAC concentration in a variety of tissues from different species we here demonstrate that the discrepancy resulted from subphysiologic NAC c oncentrations. (C) 1998 Federation of European Biochemical Societies.