Differential phosphorylation-based regulation of αB-crystallin chaperone activity for multipass transmembrane proteins
| Autor: | Simona Allocca, Michela Ciano, Lucrezia della Volpe, Maria Camilla Ciardulli, Stefano Bonatti, Massimo D'Agostino |
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| Přispěvatelé: | Ciano, Michela, Allocca, Simona, Ciardulli, Maria Camilla, Della Volpe, Lucrezia, Bonatti, Stefano, D'Agostino, Massimo |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Protein Folding DNA Complementary Green Fluorescent Proteins Biophysics Biology TMP transmembrane protein Biochemistry Article CRYAB αB-crystallin ER endoplasmic reticulum Serine 03 medical and health sciences 0302 clinical medicine Multipass transmembrane proteins Chaperone activity Cell Line Tumor Heat shock protein Humans Phosphorylation Molecular Biology Multipass transmembrane protein Endoplasmic reticulum Membrane Proteins alpha-Crystallin B Chain Cell Biology Transmembrane protein Cell biology Folding (chemistry) Cytosol 030104 developmental biology αB-crystallin/HspB5/CRYAB Mutagenesis 030220 oncology & carcinogenesis Mutation FEVR Familial exudative vitreoretinopathy MAPK mitogen-activated protein kinase sHsp small heat shock protein Biogenesis Molecular Chaperones Plasmids Protein Binding Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2016.09.071 |
| Popis: | We have previously shown that αB-crystallin (CRYAB), a small heat shock protein (sHsp) that prevents irreversible aggregation of unfolded protein by an ATP-independent chaperone activity, plays a pivotal role in the biogenesis of multipass transmembrane proteins (TMPs) assisting their folding from the cytosolic side of the endoplasmic reticulum (ER) (D'Agostino et al., 2013). Here we present evidence, based on phosphomimetic substitutions, that the three phosphorytable serine residues at position 19, 45 and 59 of CRYAB play a different regulatory role in this novel chaperone activity: S19 and S45 have a strong inhibitory effect, either alone or in combination, while S59 has not and counteracts the inhibition caused by single phosphomimetic substitutions at S19 and S45. Interestingly, all phosphomimetic substitutions determine the formation of smaller oligomeric complexes containing CRYAB, indicating that the inhibitory effect seen for S19 and S45 cannot be ascribed to the reduction of oligomerization frequently associated to a decreased chaperone activity. These results indicate that phosphorylation finely regulates the chaperone activity of CRYAB with multipass TMPs and suggest a pivotal role for S59 in this process. Highlights • CRYAB chaperone activity toward ATP7B-H1069Q and Fz4-FEVR. • Phosphomimetic S19D and S45D inhibit CRYAB chaperone activity. • Phosphomimetic S59D protects CRYAB chaperone activity. • Pseudo-phosphorylation decreases CRYAB oligomerization. |
| Databáze: | OpenAIRE |
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