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Pseudophosphorylation of single residues of the J‐domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system.
- Source :
- Protein Science: A Publication of the Protein Society; Aug2024, Vol. 33 Issue 8, p1-17, 17p
- Publication Year :
- 2024
-
Abstract
- The Hsp70 system is essential for maintaining protein homeostasis and comprises a central Hsp70 and two accessory proteins that belong to the J‐domain protein (JDP) and nucleotide exchange factor families. Posttranslational modifications offer a means to tune the activity of the system. We explore how phosphorylation of specific residues of the J‐domain of DNAJA2, a class A JDP, regulates Hsc70 activity using biochemical and structural approaches. Among these residues, we find that pseudophosphorylation of Y10 and S51 enhances the holding/folding balance of the Hsp70 system, reducing cochaperone collaboration with Hsc70 while maintaining the holding capacity. Truly phosphorylated J domains corroborate phosphomimetic variant effects. Notably, distinct mechanisms underlie functional impacts of these DNAJA2 variants. Pseudophosphorylation of Y10 induces partial disordering of the J domain, whereas the S51E substitution weakens essential DNAJA2‐Hsc70 interactions without a large structural reorganization of the protein. S51 phosphorylation might be class‐specific, as all cytosolic class A human JDPs harbor a phosphorylatable residue at this position. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09618368
- Volume :
- 33
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Protein Science: A Publication of the Protein Society
- Publication Type :
- Academic Journal
- Accession number :
- 178683468
- Full Text :
- https://doi.org/10.1002/pro.5105