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Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding

Author

Listed:
  • Yan Chen

    (Tsinghua University
    Peking University)

  • Bin Tsai

    (Peking University)

  • Ningning Li

    (Peking University)

  • Ning Gao

    (Peking University
    Peking University
    Changping Laboratory)

Abstract

Ribosome associated complex (RAC), an obligate heterodimer of HSP40 and HSP70 (Zuo1 and Ssz1 in yeast), is conserved in eukaryotes and functions as co-chaperone for another HSP70 (Ssb1/2 in yeast) to facilitate co-translational folding of nascent polypeptides. Many mechanistic details, such as the coordination of one HSP40 with two HSP70s and the dynamic interplay between RAC-Ssb and growing nascent chains, remain unclear. Here, we report three sets of structures of RAC-containing ribosomal complexes isolated from Saccharomyces cerevisiae. Structural analyses indicate that RAC on the nascent-chain-free ribosome is in an autoinhibited conformation, and in the presence of a nascent chain at the peptide tunnel exit (PTE), RAC undergoes large-scale structural remodeling to make Zuo1 J-Domain more accessible to Ssb. Our data also suggest a role of Zuo1 in orienting Ssb-SBD proximal to the PTE for easy capture of the substrate. Altogether, in accordance with previous data, our work suggests a sequence of structural remodeling events for RAC-Ssb during co-translational folding, triggered by the binding and passage of growing nascent chain from one to another.

Suggested Citation

  • Yan Chen & Bin Tsai & Ningning Li & Ning Gao, 2022. "Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31127-4
    DOI: 10.1038/s41467-022-31127-4
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    1. Marius A. Klein & Klemens Wild & Miglė Kišonaitė & Irmgard Sinning, 2024. "Methionine aminopeptidase 2 and its autoproteolysis product have different binding sites on the ribosome," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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