A persulfidation-based mechanism controls aquaporin-8 conductance
| العنوان: | A persulfidation-based mechanism controls aquaporin-8 conductance |
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| المؤلفون: | Roberto Sitia, Giovanna Musco, Anna Rubartelli, Andrea Orsi, Mauro Galli, Gerd Patrick Bienert, Michela Ghitti, Iria Medraño-Fernandez, Stefano Bestetti |
| المساهمون: | Bestetti, Stefano, Medraño-Fernandez, Iria, Galli, Mauro, Ghitti, Michela, Bienert, Gerd, Musco, Giovanna, Orsi, Andrea, Rubartelli, Anna, Sitia, Roberto |
| المصدر: | ResearcherID Science Advances |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | inorganic chemicals, 0301 basic medicine, Cell Membrane Permeability, Molecular Conformation, Aquaporin, Gating, Sulfides, Aquaporins, Models, Biological, Receptor tyrosine kinase, 03 medical and health sciences, chemistry.chemical_compound, Stress, Physiological, Extracellular, Amino Acid Sequence, Hydrogen Sulfide, Research Articles, Histidine, Multidisciplinary, biology, Cell Membrane, SciAdv r-articles, Biological Transport, Cell Biology, Hydrogen Peroxide, Cystathionine beta synthase, 030104 developmental biology, chemistry, biology.protein, Biophysics, Oxidation-Reduction, Nicotinamide adenine dinucleotide phosphate, Research Article, Cysteine |
| الوصف: | A two-step posttranslational modification of AQP8 provides a mechanism regulating plasma membrane H2O2 conductance. Upon engagement of tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)–oxidases release H2O2 in the extracellular space. We reported previously that aquaporin-8 (AQP8) transports H2O2 across the plasma membrane and is reversibly gated during cell stress, modulating signal strength and duration. We show that AQP8 gating is mediated by persulfidation of cysteine 53 (C53). Treatment with H2S is sufficient to block H2O2 entry in unstressed cells. Silencing cystathionine β-synthase (CBS) prevents closure, suggesting that this enzyme is the main source of H2S. Molecular modeling indicates that C53 persulfidation displaces a nearby histidine located in the narrowest part of the channel. We propose that H2O2 molecules transported through AQP8 sulfenylate C53, making it susceptible to H2S produced by CBS. This mechanism tunes H2O2 transport and may control signaling and limit oxidative stress. |
| تدمد: | 2375-2548 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ebd85229a61d8ae8dda01c80d43ed2baTest https://doi.org/10.1126/sciadv.aar5770Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ebd85229a61d8ae8dda01c80d43ed2ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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