Microtubule dysfunction by posttranslational nitrotyrosination of α-tubulin: A nitric oxide-dependent mechanism of cellular injury

摘要: NO2Tyr (3-Nitrotyrosine) is a modified amino acid that formed by nitric oxide-derived species and has been implicated in the pathology of diverse human diseases. Nitration active-site tyrosine residues known to compromise protein structure function. Although free produced abundant concentrations under pathological conditions, its capacity alter function at translational or posttranslational level unknown. Here, we report transported into mammalian cells selectively incorporated extreme carboxyl terminus α-tubulin via mechanism catalyzed enzyme tubulin–tyrosine ligase. In contrast enzymatically regulated carboxyl-terminal tyrosination/detyrosination cycle α-tubulin, incorporation shows apparent irreversibility. Nitrotyrosination induces alterations cell morphology, changes microtubule organization, loss epithelial-barrier function, intracellular redistribution motor cytoplasmic dynein. These observations imply nitrotyrosination invokes conformational changes, either directly allosteric interactions, surface-exposed compromises this critical domain regulating organization binding motor- microtubule-associated proteins. Collectively, these illustrate whereby can impact deleteriously on conditions encompassing reactive nitrogen production. The data also yield further insight role plays