Artículo
Nitration of tyrosine 74 prevents human cytochrome c to play a key role in apoptosis signaling by blocking caspase-9 activation
Autor/es | García Heredia, José Manuel
Díaz Moreno, Irene Nieto Mesa, Pedro Manuel Orzáez, Mar Kocanis, Stella Teixeira, Miguel Pérez Payá, Enrique Díaz Quintana, Antonio Jesús Rosa Acosta, Miguel Ángel de la |
Departamento | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Fecha de publicación | 2010 |
Fecha de depósito | 2019-03-28 |
Publicado en |
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Resumen | Tyrosine nitration is one of the most common post-transcriptional modifications of proteins, so affecting their structure and function. Human cytochrome c, with five tyrosine residues, is an excellent case study as it is ... Tyrosine nitration is one of the most common post-transcriptional modifications of proteins, so affecting their structure and function. Human cytochrome c, with five tyrosine residues, is an excellent case study as it is a well-known protein playing a double physiological role in different cell compartments. On one hand, it acts as electron carrier within the mitochondrial respiratory electron transport chain, and on the other hand, it serves as a cytoplasmic apoptosis-triggering agent. In a previous paper, we reported the effect of nitration on physicochemical and kinetic features of monotyrosine cytochrome c mutants. Here, we analyse the nitration-induced changes in secondary structure, thermal stability, haem environment, alkaline transition and molecular dynamics of three of such monotyrosine mutants – the so-called h-Y67, h-Y74 and h-Y97 – which have four tyrosines replaced by phenylalanines and just keep the tyrosine residue giving its number to the mutant. The resulting data, along with the functional analyses of the three mutants, indicate that it is the specific nitration of solvent-exposed Tyr74 which enhances the peroxidase activity and blocks the ability of Cc to activate caspase-9, thereby preventing the apoptosis signaling pathway. |
Identificador del proyecto | BFU2006-01361/BMC
BFU2009-07190 |
Cita | García Heredia, J.M., Díaz Moreno, I., Nieto Mesa, P.M., Orzáez, M., Kocanis, S., Teixeira, M.,...,Rosa Acosta, M.Á.d.l. (2010). Nitration of tyrosine 74 prevents human cytochrome c to play a key role in apoptosis signaling by blocking caspase-9 activation. BBA - Bioenergetics, 1797 (6-7), 981-993. |
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