Chaperone Function of Hgh1 in the Biogenesis of Eukaryotic Elongation Factor 2.
Eukaryotic elongation factor 2 (eEF2) is an abundant and essential component of the translation machinery. The biogenesis of this 93Â kDa multi-domain protein is assisted by the chaperonin TRiC/CCT. Here, we show in yeast cells that the highly conserved protein Hgh1 (FAM203 in humans) is a chaperone that cooperates with TRiC ... in eEF2 folding. In the absence of Hgh1, a substantial fraction of newly synthesized eEF2 is degraded or aggregates. We solved the crystal structure of Hgh1 and analyzed the interaction of wild-type and mutant Hgh1 with eEF2. These experiments revealed that Hgh1 is an armadillo repeat protein that binds to the dynamic central domain III of eEF2 via a bipartite interface. Hgh1 binding recruits TRiC to the C-terminal eEF2 module and prevents unproductive interactions of domain III, allowing efficient folding of the N-terminal GTPase module. eEF2 folding is completed upon dissociation of TRiC and Hgh1.
Mesh Terms:
Models, Molecular, Molecular Chaperones, Mutation, Peptide Elongation Factor 2, Protein Binding, Protein Folding, Protein Interaction Domains and Motifs, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Structure-Activity Relationship
Models, Molecular, Molecular Chaperones, Mutation, Peptide Elongation Factor 2, Protein Binding, Protein Folding, Protein Interaction Domains and Motifs, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Structure-Activity Relationship
Mol. Cell
Date: Dec. 04, 2018
PubMed ID: 30876804
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