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Title | Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 3410, Year 2022 |
Publish date | Jun 14, 2022 |
Authors | Yan Chen / Bin Tsai / Ningning Li / Ning Gao / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:35701497 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 - 6.0 Å |
Structure data | EMDB-32975: Cryo-EM structure of endogenous 80S-RAC complex from S. cerevisiae EMDB-32977: Cryo-EM structure of RNC-RAC complex in presence of Ssb from S. cerevisiae 1 EMDB-32978, PDB-7x34: EMDB-32988: Cryo-EM structure of RNC-RAC complex (State C2) EMDB-32991, PDB-7x3k: |
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Keywords | TRANSLATION/RNA / RAC / co-translational folding / TRANSLATION / TRANSLATION-RNA complex |