Fine Tuning: Effects of Post-Translational Modification on Hsp70 Chaperones

• Published in: International journal of molecular sciences Vol. 20; no. 17; p. 4207
• Main Authors: Griffith, Alijah A, Holmes, William
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-08-2019; MDPI
• Subjects: Adenosine triphosphatase; Allosteric Regulation; Amino acids; Animals; Binding; Binding sites; chaperone proteins; Chaperones; Cytoplasm; Domains; Endoplasmic reticulum; Enzymes; Gene expression; Hsp70; HSP70 Heat-Shock Proteins - chemistry; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; Humans; Hydrophobicity; Localization; Lysine; Nucleotides; Phosphorylation; Polarity; Post-translation; post-translational modifications; Protein folding; Protein Processing, Post-Translational; Proteins; Residues; Review; Structure-function relationships; Translation; Ubiquitin; chaperone proteins; Hsp70; post-translational modifications
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20174207

The discovery of heat shock proteins shaped our view of protein folding in the cell. Since their initial discovery, chaperone proteins were identified in all domains of life, demonstrating their vital and conserved functional roles in protein homeostasis. Chaperone proteins maintain proper protein folding in the cell by utilizing a variety of distinct, characteristic mechanisms to prevent aberrant intermolecular interactions, prevent protein aggregation, and lower entropic costs to allow for protein refolding. Continued study has found that chaperones may exhibit alternative functions, including maintaining protein folding during endoplasmic reticulum (ER) import and chaperone-mediated degradation, among others. Alternative chaperone functions are frequently controlled by post-translational modification, in which a given chaperone can switch between functions through covalent modification. This review will focus on the Hsp70 class chaperones and their Hsp40 co-chaperones, specifically highlighting the importance of post-translational control of chaperones. These modifications may serve as a target for therapeutic intervention in the treatment of diseases of protein misfolding and aggregation.