Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation
| Autor: | Ashleigh Bachman, Geoffrey M. Gray, Ioannis Gelis, Michael A. Moses, Radwan Ebna Noor, Dimitra Keramisanou, Len Neckers, Kristin Beebe, M V Vasantha Kumar, Arjan van der Vaart, Wanping Xu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
inorganic chemicals Protein Folding Chaperonins Science Population General Physics and Astronomy Cell Cycle Proteins macromolecular substances SH2 domain environment and public health General Biochemistry Genetics and Molecular Biology Article src Homology Domains 03 medical and health sciences Humans HSP90 Heat-Shock Proteins Phosphorylation lcsh:Science education Protein kinase A education.field_of_study Multidisciplinary biology Chemistry Kinase General Chemistry Protein-Tyrosine Kinases 3. Good health Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology CDC37 Chaperone (protein) biology.protein Chaperone complex bacteria lcsh:Q |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) |
| ISSN: | 2041-1723 |
| Popis: | During the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically regulates its interaction with Cdc37 and thus affects the chaperoning of only protein kinase clients. In summary, we find that by providing client class specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client recruitment but also shape the post-translational modification landscape of Hsp90 in a client class-specific manner. The Hsp90 chaperone cycle is influenced by multiple phosphorylation events but their regulatory functions are poorly understood. Here, the authors show that phosphorylation and unfolding of cochaperone Cdc37 tailors the Hsp90 chaperone cycle by recruiting kinases that promote distinct phosphorylation patterns. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|