# The cotranslational cycle of the ribosome-bound Hsp70 homolog Ssb

## TL;DR

The paper reveals how the ribosome-bound Hsp70 homolog Ssb interacts with the ribosome and nascent chains during protein synthesis.

## Contribution

The study provides new structural and mechanistic insights into the cotranslational cycle of the ribosome-bound Ssb chaperone.

## Key findings

- Cryo-EM structures identify Rpl25/uL23 as the ribosomal binding site for Ssb.
- Ssb's substrate binding domain is positioned near the ribosome tunnel exit to receive nascent chains.
- Ssb undergoes conformational changes during ATP hydrolysis without clashing with the ribosome.

## Abstract

Coupling of ribosomal translation with cotranslational protein folding is essential for cellular homeostasis. In eukaryotes, Hsp70 and its J-domain cochaperone, the heterodimeric ribosome-associated complex (RAC), are central to this process; however, mechanistic insights into the coordination of Hsp70 function with translation remain limited. Here, we present two cryo-EM structures of the ribosome-bound yeast Hsp70 Ssb, identifying Rpl25/uL23 as the ribosomal binding site and revealing its interaction with a model nascent chain. Together with detailed biochemical and mutational analyses, these structures enable us to delineate the intricate RAC-dependent cycle, which positions the substrate binding domain of Ssb-ATP close to the tunnel exit to receive nascent chains. This arrangement allows Ssb to undergo substantial conformational changes upon ATP hydrolysis without steric clashes with the ribosome, while the substrate binding domain of Ssb, now anchored by the tightly bound nascent chain, remains close to the tunnel exit.

Ribosomal translation is coupled to cotranslational protein folding, process assisted by dedicated chaperones. Here, authors present structures of the ribosome-bound yeast Hsp70 chaperone Ssb, identifying its ribosomal binding site and revealing its interactions with a model nascent chain.