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Financement de l’UE (211 755 €) : Percée dans un mécanisme d’activation à longue portée de l’enzyme radicalaire glycyle Hor 06/05/2024 Programme de recherche et d'innovation de l'UE « Horizon »
Vue d’ensemble
Texte
Percée dans un mécanisme d’activation à longue portée de l’enzyme radicalaire glycyle
Glycyl radical enzymes (GREs) are one of the most prominent biological catalysts in both strict and facultative anaerobes. They are responsible for a broad range of radical-based chemistry and catalyse reactions involved in diverse metabolic pathways such as acid fermentation, DNA synthesis and the anaerobic metabolism of pollutants. GREs are activated by members of the S-adenosylmethionine (SAM) radical family. Activation of GREs requires the formation of a protein-protein activation complex with the small GRE-AE. All known structures of GREs show that a major conformational change very likely occurs during the glycyl radical generation upon interaction with the GRE-AE. Only a structure of a GRE:AE holocomplex would shed light on the unprecedented conformational changes involved in GRE activation. Glycyl radicals and iron-sulfur clusters are extremely oxygen sensitive, rendering the proteins challenging to work with. GREAM will narrow a significant knowledge gap by studying the anaerobic class III RNR natural fusion (NrdD:NrdG). In order to study the mechanism of activation, GREAM will use an integrative research approach combining biochemical, biophysical and cryo-EM – assisted by X-ray crystallography. With my experience in anaerobic protein characterisation and crystallisation, I will join the Fontecave lab to build up on their experience in spectroscopic characterisation of oxygen-sensitive protein complexes and achieve the first aim or GREAM. During a secondment in the Logan lab, who are expert in structural characterisation of aRNRs and have a long lasting collaboration with the host, I will solve the anaerobic cryo-EM structure of the NrdD:NrdG holocomplex and achieve the final goal of GREAM. This newly established international collaboration will permit combining integrative approaches to successfully answer all GREAM’s questions and allow me to acquire invaluable experience in my future career.
| Lunds Universitet | ? |
| College de France | 211 755 € |
https://cordis.europa.eu/project/id/101153288
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : Lunds Universitet, Lund, Suède.
