A protein complex required for signal-sequence-specific sorting and translocation.
We have purified a nascent-polypeptide-associated complex (NAC) which prevents short ribosome-associated nascent polypeptides from inappropriate interactions with proteins in the cytosol. NAC binds nascent-polypeptide domains emerging from ribosomes unless a signal peptide is fully exposed. Depletion of cytosolic proteins (including NAC) from ribosomes carrying nascent polypeptides allows the signal recognition particle (SRP) to crosslink to polypeptides irrespective of whether or not they contain signal peptides. In the absence of cytosol, proteins lacking signal peptides can be mistranslocated into the endoplasmic reticulum in vitro, albeit with low efficiency. Readdition of NAC restores the specificity of SRP and fidelity of translocation.
Wiedmann
B
B
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Sakai
H
H
Davis
T A
TA
Wiedmann
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D003432:Cross-Linking Reagents; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D018271:Signal Recognition Particle / Q000378:metabolism
D003432:Cross-Linking Reagents; D010455:Peptides; D021382:Protein Sorting Signals; D011506:Proteins; D018271:Signal Recognition Particle