Nyathi and Pool describe how a chaperone complex helps ensure nascent polypeptides are correctly processed as they emerge from ribosomes.
Newly synthesized proteins must be quickly modified, folded, and targeted to their correct destination within the cell. Many of the factors responsible for these processing steps bind to the same “universal adaptor site” (UAS) on ribosomes, allowing them to target nascent polypeptides as soon as they emerge. How the binding of these factors is coordinated so that each polypeptide gets processed correctly remains unclear.
Nyathi and Pool found that Map1, a budding yeast enzyme that cleaves the N-terminal methionine off of most cytosolic proteins, also binds to the UAS, adjacent to the α subunit of a ribosome-associated chaperone complex called NAC. Overexpressing Map1 displaced the signal recognition particle (SRP), which guides nascent secretory and membrane proteins to the ER, suggesting that Map1 and SRP compete for a binding site within the UAS.
Overexpressing SRP, however, failed to displace Map1 from ribosomes unless the researchers removed NAC—particularly its β subunit—from the cells. Under these circumstances, cytosolic proteins retained their N-terminal methionines and formed insoluble aggregates, indicating that NAC regulates the competition between Map1 and SRP by suppressing the latter complex’s association with the UAS.
Yet NAC’s α subunit can assist the SRP in translocating secretory proteins to the ER. At low temperatures, or when SRP levels are diminished, nascent secretory polypeptides go unrecognized, causing them to aggregate and inhibit cell growth. These defects were exacerbated by the loss of NAC’s α subunit, and alleviated by its overexpression. The authors think that conformational changes in the ribosome and/or NAC in response to the presence or absence of a nascent secretory polypeptide might determine whether SRP binding is promoted or suppressed.
Text by Ben Short