Unknown

Dataset Information

0

Structural analysis of the ribosome-associated complex (RAC) reveals an unusual Hsp70/Hsp40 interaction.


ABSTRACT: Yeast Zuotin and Ssz are members of the conserved Hsp40 and Hsp70 chaperone families, respectively, but compared with canonical homologs, they atypically form a stable heterodimer termed ribosome-associated complex (RAC). RAC acts as co-chaperone for another Hsp70 to assist de novo protein folding. In this study, we identified the molecular basis for the unusual Hsp70/Hsp40 pairing using amide hydrogen exchange (HX) coupled with mass spectrometry and mutational analysis. Association of Ssz with Zuotin strongly decreased the conformational dynamics mainly in the C-terminal domain of Ssz, whereas Zuotin acquired strong conformational stabilization in its N-terminal segment. Deletion of the highly flexible N terminus of Zuotin abolished stable association with Ssz in vitro and caused a phenotype resembling the loss of Ssz function in vivo. Thus, the C-terminal domain of Ssz, the N-terminal extension of Zuotin, and their mutual stabilization are the major structural determinants for RAC assembly. We furthermore found dynamic changes in the J-domain of Zuotin upon complex formation that might be crucial for RAC co-chaperone function. Taken together, we present a novel mechanism for converting Zuotin and Ssz chaperones into a functionally active dimer.

SUBMITTER: Fiaux J 

PROVIDER: S-EPMC2823442 | BioStudies | 2010-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2005-01-01 | S-EPMC1177401 | BioStudies
2019-01-01 | S-EPMC6519820 | BioStudies
2020-01-01 | S-EPMC7083937 | BioStudies
2017-01-01 | S-EPMC5563141 | BioStudies
2010-01-01 | S-EPMC2938849 | BioStudies
1999-01-01 | S-EPMC104411 | BioStudies
2010-01-01 | S-EPMC2998361 | BioStudies
2010-01-01 | S-EPMC2950966 | BioStudies
2020-01-01 | S-EPMC7148561 | BioStudies
2013-01-01 | S-EPMC3727329 | BioStudies