Cracking the chaperone code through the computational microscope Review
| Authors: | Guarra, F.; Sciva, C.; Bonollo, G.; Pasala, C.; Chiosis, G.; Moroni, E.; Colombo, G. |
| Review Title: | Cracking the chaperone code through the computational microscope |
| Abstract: | The heat shock protein 90 kDa (Hsp90) chaperone machinery plays a crucial role in maintaining cellular homeostasis. Beyond its traditional role in protein folding, Hsp90 is integral to key pathways influencing cellular function in health and disease. Hsp90 operates through the modular assembly of large multiprotein complexes, with their composition, stability, and localization adapting to the cell's needs. Its functional dynamics are finely tuned by ligand binding and post-translational modifications (PTMs). Here, we discuss how to disentangle the intricacies of the complex code that governs the crosstalk between dynamics, binding, PTMs, and the functions of the Hsp90 machinery using computer-based approaches. Specifically, we outline the contributions of computational and theoretical methods to the understanding of Hsp90 functions, ranging from providing atomic-level insights into its dynamics to clarifying the mechanisms of interactions with protein clients, cochaperones, and ligands. The knowledge generated in this framework can be actionable for the design and development of chemical tools and drugs targeting Hsp90 in specific disease-associated cellular contexts. Finally, we provide our perspective on how computation can be integrated into the study of the fine-tuning of functions in the highly complex Hsp90 landscape, complementing experimental methods for a comprehensive understanding of this important chaperone system. © 2024 The Authors |
| Keywords: | controlled study; review; nonhuman; cell function; drug development; protein processing; heat shock protein 90; protein folding; homeostasis; dynamics; ligand binding; chaperone; multiprotein complex; microscope; human; hsp; chaperone code; functional assemblies |
| Journal Title: | Cell Stress & Chaperones |
| Volume: | 29 |
| Issue: | 5 |
| ISSN: | 1355-8145 |
| Publisher: | Springer |
| Date Published: | 2024-10-01 |
| Start Page: | 626 |
| End Page: | 640 |
| Language: | English |
| DOI: | 10.1016/j.cstres.2024.08.001 |
| PUBMED: | 39142378 |
| PROVIDER: | scopus |
| PMCID: | PMC11399801 |
| DOI/URL: | |
| Notes: | Review -- Source: Scopus |
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