Fig. 7: Model of RAC-Ssb actions in co-translational folding.
From: Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding
a, b RAC binds to the 80S ribosome, and through interactions of Zuo1 ZHD with H24-eL31-H101 (H24 as a key anchor point) on the 60S subunit and Zuo1 CTD with ES12-h44 on the 40S subunit. The JD of Zuo1 is initially covered by Ssz1 SBD. During translation elongation, the nascent chain emerges from the PTE (∼5 residues) and starts to interact with the hydrophobic patch on the N-terminus of ZHD-α3. c The elongated nascent chain triggers extensive conformational remodeling of RAC and Ssz1 is relocated to the PTE side of Zuo1 JD. A handover of substrate from Zuo1 to Ssz1 also occurs, which leads to further weakening of the Ssz1:Zuo1 interface. d The nascent chain competitively binds to Ssz1 SBD and thus disrupts the interface between Zuo1 and Ssz1 to mobilize Ssz1, resulting in a full exposure of the HPD motif. e Ssb-ATP recognizes Zuo1 JD and thus is recruited to the translating ribosome, with its SBD facing the PTE. f The nascent chain is handed over from RAC to Ssb. The ATP-hydrolysis of Ssb takes place, facilitated by Zuo1 JD, and Ssb transits to the ADP and high-affinity substrate-bound conformation.
