Société Française de Biochimie et Biologie Moléculaire


Lionel TARRAGO - Year 2015

AMU Institut des Sciences Moléculaires de Marseille
Monitoring methionine sulfoxide with stereospecific mechanism-based fluorescent sensors. Nat Chem Biol. 2015 May;11(5):332-8.
Tarrago L, Péterfi Z, Lee BC, Michel T, Gladyshev VN

 

Cv

Lionel Tarrago, 34 ans, s’intéresse aux processus d’oxydation et réduction des protéines dans les organismes. Il a effectué une thèse de doctorat en biologie végétale au CEA de Cadarache sous la direction du Dr. Pascal Rey. Son travail a porté sur la caractérisation des systèmes enzymatiques chloroplastiques responsables de la protection des protéines chez Arabidopsis thaliana en réponse aux stress oxydants. Ses recherches ont notamment permis de déterminer les mécanismes moléculaires des systèmes de réparation des méthionines oxydées. Il a ensuite rejoint le laboratoire du Pr. Vadim Gladyshev à la faculté de médecine d’Harvard à Boston aux Etats-Unis pour y développer des biosenseurs capables de suivre et quantifier de manière dynamique le contenu en méthionines oxydées des protéines. Les deux senseurs fluorescents présentés dans l’article sont utilisables pour suivre l’évolution de l’oxydation des protéines in vivo. Il occupe actuellement un poste d’attaché temporaire à l’enseignement et à la recherche dans le laboratoire du Dr. Marius Réglier (iSm2) où son travail de recherche consiste à développer un système de catalyse hétérogène enzyme-complexe métallique.

Contact

Lionel Tarrago
AMU Institut des Sciences Moléculaires de Marseille
Service 342 - Campus Scientifique de St Jérôme
13397 Marseille cedex 20
This email address is being protected from spambots. You need JavaScript enabled to view it.

Résumé de l'article

Methionine can be reversibly oxidized to methionine sulfoxide (MetO) under physiological and pathophysiological conditions, but its use as a redox marker suffers from the lack of tools to detect and quantify MetO within cells. In this work, we created a pair of complementary stereospecific genetically encoded mechanism-based ratiometric fluorescent sensors of MetO by inserting a circularly permuted yellow fluorescent protein between yeast methionine sulfoxide reductases and thioredoxins. The two sensors, respectively named MetSOx and MetROx for their ability to detect S and R forms of MetO, were used for targeted analysis of protein oxidation, regulation and repair as well as for monitoring MetO in bacterial and mammalian cells, analyzing compartment-specific changes in MetO and examining responses to physiological stimuli.Methionine can be reversibly oxidized to methionine sulfoxide (MetO) under physiological and pathophysiological conditions, but its use as a redox marker suffers from the lack of tools to detect and quantify MetO within cells. In this work, we created a pair of complementary stereospecific genetically encoded mechanism-based ratiometric fluorescent sensors of MetO by inserting a circularly permuted yellow fluorescent protein between yeast methionine sulfoxide reductases and thioredoxins. The two sensors, respectively named MetSOx and MetROx for their ability to detect S and R forms of MetO, were used for targeted analysis of protein oxidation, regulation and repair as well as for monitoring MetO in bacterial and mammalian cells, analyzing compartment-specific changes in MetO and examining responses to physiological stimuli.Methionine can be reversibly oxidized to methionine sulfoxide (MetO) under physiological and pathophysiological conditions, but its use as a redox marker suffers from the lack of tools to detect and quantify MetO within cells. In this work, we created a pair of complementary stereospecific genetically encoded mechanism-based ratiometric fluorescent sensors of MetO by inserting a circularly permuted yellow fluorescent protein between yeast methionine sulfoxide reductases and thioredoxins. The two sensors, respectively named MetSOx and MetROx for their ability to detect S and R forms of MetO, were used for targeted analysis of protein oxidation, regulation and repair as well as for monitoring MetO in bacterial and mammalian cells, analyzing compartment-specific changes in MetO and examining responses to physiological stimuli.