Interplay between Ero1 and PDI on oxidative protein folding in the endoplasmic reticulum
Il 13/04/2015 ore 14.30 - 15.30
Sala conferenze CNR, Area della Ricerca Na1, Via P. Castellino, 111 80131 Napoli
Dr Lei Wang will give a seminar on Ero1 flavoproteins that catalyze oxidative folding in the endoplasmic reticulum (ER), consuming oxygen and generating hydrogen peroxide (H2O2). The ER-localized glutathione peroxidase 7 (GPx7) shows protein disulfide isomerase (PDI)-dependent peroxidase activity in vitro. His work aims at identifying the physiological role of GPx7 in the Ero1α/PDI oxidative folding pathway and at dissecting the reaction mechanisms of GPx7. His results show that GPx7 can utilize Ero1α-produced H2O2 to accelerate oxidative folding of substrates both in vitro and in vivo. H2O2 oxidizes Cys57 of GPx7 to sulfenic acid, which can be resolved by Cys86 to form an intramolecular disulfide bond. Both the disulfide form and sulfenic acid form of GPx7 can oxidize PDI for catalyzing oxidative folding. GPx7 prefers to interact with the a domain of PDI, and intramolecular cooperation between the two redox-active sites of PDI increases the activity of the Ero1α/GPx7/PDI triad. In vitro and in vivo evidence provide mechanistic insights into how cells consume potentially harmful H2O2 while optimizing oxidative protein folding via the Ero1α/GPx7/PDI triad. Cys57 can promote PDI oxidation in two ways, and Cys86 emerges as a novel noncanonical resolving cysteine. GPx7 promotes oxidative protein folding, directly utilizing Ero1α-generated H2O2 in the early secretory compartment. Thus, the Ero1α/GPx7/PDI triad generates two disulfide bonds and two H2O molecules at the expense of a single O2 molecule
Dr Lei Wang is currently Associate Research Scientist at the National Laboratory of Biomacromolecules
Institute of Biophysics, Chinese Academy of Sciences in Beijing, China.
Organizzato da:
Ibp-Cnr
Referente organizzativo:
Alberto Luini
CNR - Istituto di biochimica delle proteine
a.luini@ibp.cnr.it
081/6132535
Modalità di accesso: ingresso libero