The ribosome-bound Hsp70 homolog Ssb of Saccharomyces cerevisiae

Abstract

The Hsp70 homolog Ssb directly binds to the ribosome and contacts a variety of newly synthesized polypeptide chains as soon as they emerge from the ribosomal exit tunnel. For this reason a general role of Ssb in the de novo folding of newly synthesized proteins is highly suggestive. However, for more than a decade client proteins which require Ssb for proper folding have remained elusive. It was therefore speculated that Ssb, despite its ability to interact with a large variety of nascent polypeptides, may assist the folding of only a small and specific subset. Alternatively, it has been suggested that Ssb's function may be limited to the protection of nascent polypeptides from aggregation until downstream chaperones take over and actively fold their substrates. There is also evidence that Ssb, in parallel to a classical chaperone function, is involved in the regulation of cellular signaling processes. Here we aim to summarize what is currently known about Ssb's multiple functions and what remains to be ascertained by future research.

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

“…However, due to mixed effects on elongation and termination, ribosomal transit time in the ⌬ssb1 ⌬ssb2 ⌬asc1 strain resembled that of the wild type. This model is also consistent with the finding that ⌬zuo1 and ⌬ssb1 ⌬ssb2 strains are highly sensitive to aminoglycosides, which affect both elongation and termination, but do not display increased sensitivity toward the elongation inhibitor CHX (23,33,35). Of note, growth inhibition curves, as performed in this work, take into account the fact that ⌬zuo1 and ⌬ssb1⌬ssb2 strains display slow growth at 30°C.…”

“…We thus tested whether polysomes were stabilized in the absence of RAC/Ssb. As previously reported (33,35), the polysome content of the ⌬ssb1 ⌬ssb2 strain was lower than that of the wild-type strain (Fig. 8A and B, left panels).…”

“…The temperature shift was performed to enhance effects due to the absence of RAC/Ssb. The ⌬ssb1 ⌬ssb2 mutation causes severe cold sensitivity (33). Cells were then harvested in the presence or absence of cycloheximide (CHX) as indicated.…”

“…Yeast possesses a ribosome-bound chaperone triad consisting of the Hsp70 homologs Ssb1 and Ssb2 (collectively termed Ssb), Ssz1, and the J-domain protein Zuo1 (33). Zuo1 and Ssz1 form a stable complex, termed the ribosome-associated complex (RAC) (34).…”

Biology of the Heat Shock Response and Protein Chaperones: Budding Yeast (Saccharomyces cerevisiae) as a Model System

“…This mechanism could explain the observed pleiotropic cation sensitivity of cells lacking Ssb1/2 (349). Two possible models to account for the observed interaction between Ssb and the SNF pathway have been proposed (337). The first model is that Ssb has a K m for ATP binding approximately 1,000 times higher than that of Ssa; in addition, the ATP hydrolysis rate is 50 times higher, which, taken together, suggest that Ssb might sense ATP levels to influence this pathway.…”