Related Experiment Video
Updated: Mar 2, 2026

Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
Published on: March 24, 2019
An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in
Abbey D Zuehlke1, Michael Reidy2, Coney Lin2
1Urologic Oncologic Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
Abstract:
Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone. To properly chaperone its clientele, Hsp90 proceeds through an ATP-dependent conformational cycle influenced by posttranslational modifications (PTMs) and assisted by a number of co-chaperone proteins. Although Hsp90 conformational changes in solution have been well-studied, regulation of these complex dynamics in cells remains unclear. Phosphorylation of human Hsp90α at the highly conserved tyrosine 627 has previously been reported to reduce client interaction and Aha1 binding. Here we report that these effects are due to a long-range conformational impact inhibiting Hsp90α N-domain dimerization and involving a region of the middle domain/carboxy-terminal domain interface previously suggested to be a substrate binding site. Although Y627 is not phosphorylated in yeast, we demonstrate that the non-conserved yeast co-chaperone, Hch1, similarly affects yeast Hsp90 (Hsp82) conformation and function, raising the possibility that appearance of this PTM in higher eukaryotes represents an evolutionary substitution for HCH1.
Related Concept Videos
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Molecular Chaperones and Protein Folding
The...
Bacterial Protein Maturation
Export of Misfolded Proteins out of the ER
Post-translational Translocation of Proteins to the RER
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...

