Quantitative assessment of chaperone binding to amyloid aggregates identifies specificity of Hsp40 interaction with yeast prion fibrils
| Autor: | Yury A. Barbitoff, Andrew G. Matveenko, Stanislav A. Bondarev, Galina A. Zhouravleva, Evgeniia M Maksiutenko, Alexandra V Kulikova |
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| Rok vydání: | 2020 |
| Předmět: |
Amyloid
Prions Protein aggregation Fibril Applied Microbiology and Biotechnology Microbiology Fungal Proteins 03 medical and health sciences Yeasts Overproduction 030304 developmental biology 0303 health sciences biology 030302 biochemistry & molecular biology General Medicine HSP40 Heat-Shock Proteins Yeast Protein Transport Cytosol Chaperone (protein) biology.protein Chaperone binding Biophysics Protein folding Molecular Chaperones Protein Binding |
| Zdroj: | FEMS Yeast Research. 20 |
| ISSN: | 1567-1364 1567-1356 |
| DOI: | 10.1093/femsyr/foaa025 |
| Popis: | Yeast self-perpetuating protein aggregates (yeast prions) provide a framework to investigate the interaction of misfolded proteins with the protein quality control machinery. The major component of this system that facilitates propagation of all known yeast amyloid prions is the Hsp104 chaperone that catalyzes fibril fragmentation. Overproduction of Hsp104 cures some yeast prions via a fragmentation-independent mechanism. Importantly, major cytosolic chaperones of the Hsp40 group, Sis1 and Ydj1, oppositely affect yeast prion propagation, and are capable of stimulating different activities of Hsp104. In this work, we developed a quantitative method to investigate the Hsp40 binding to amyloid aggregates. We demonstrate that Sis1 binds fibrils formed by the Sup35NM protein with higher affinity compared to Ydj1. Moreover, the interaction of Sis1 with the fibrils formed by the other yeast prion protein, Rnq1, is orders of magnitude weaker. We show that the deletion of the dimerization domain of Sis1 (crucial for the curing of [PSI+] by excess Hsp104) decreases its affinity to both Sup35NM and Rnq1 fibrils. Taken together, these results suggest that tight binding of Hsp40 to the amyloid fibrils is likely to enhance aggregate malpartition instead of fibril fragmentation. |
| Databáze: | OpenAIRE |
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