An unexpected role for the yeast nucleotide exchange factor Sil1 as a reductant acting on the molecular chaperone BiP
| Autor: | Kevin D Siegenthaler, Jie Wang, Kristeen A Pareja, Carolyn S. Sevier |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins genetic structures BiP QH301-705.5 Science Saccharomyces cerevisiae S. cerevisiae macromolecular substances Kar2 Biochemistry General Biochemistry Genetics and Molecular Biology Hsp70 Fungal Proteins Nucleotide exchange factor 03 medical and health sciences Stress Physiological Nucleotide Exchange Factor SIL1 oxidative stress HSP70 Heat-Shock Proteins Cysteine Biology (General) redox signaling Fungal protein General Immunology and Microbiology biology General Neuroscience Endoplasmic reticulum Membrane Transport Proteins Cell Biology General Medicine biology.organism_classification Cell biology endoplasmic reticulum 030104 developmental biology Chaperone (protein) biology.protein Medicine Research Advance Oxidation-Reduction Sil1 glutathionylation |
| Zdroj: | eLife, Vol 6 (2017) eLife |
| Popis: | Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we demonstrated that the chaperone BiP is a sensor of overly oxidizing ER conditions. We showed that modification of a conserved BiP cysteine during stress beneficially alters BiP chaperone activity to cope with suboptimal folding conditions. How this cysteine is reduced to reestablish 'normal' BiP activity post-oxidative stress has remained unknown. Here we demonstrate that BiP's nucleotide exchange factor – Sil1 – can reverse BiP cysteine oxidation. This previously unexpected reductant capacity for yeast Sil1 has potential implications for the human ataxia Marinesco-Sjögren syndrome, where it is interesting to speculate that a disruption in ER redox-signaling (due to genetic defects in SIL1) may influence disease pathology. DOI: http://dx.doi.org/10.7554/eLife.24141.001 |
| Databáze: | OpenAIRE |
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