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Etude du mécanisme de polymérisation des protéines du complexe ESCRT-III

Abstract : The ESCRT machinery (Endosomal Sorting Complexes Required for Transport) is involved in several fundamental cellular processes requiring a membrane remodeling activity such as separation of daughter cells during cytokinesis or cargo protein sorting to the lysosome. This machinery is also hijacked by many enveloped viruses such as HIV to terminate budding.The ESCRT-III complex (composed of CHMP proteins) catalyzes the membrane severing reaction by forming polymers at the membrane neck. In order to understand how those polymers are formed, the cryo-electron microscopy structure of CHMP2A/CHMP3 heteropolymers has been solved at a resolution of 22.4 Å. Details regarding the interaction mechanism between CHMP2A, CHMP3 and CHMP4B have also been obtained, notably by means of the SPR technique.Finally, to visualize ESCRT-III polymers in cells, several methods including Phage Display have been employed to get a polymer-specific antibody. This work enabled to obtain an anti-CHMP4B antibody.Overall, the results presented in this manuscript are in good agreement with the existing literature and allow to generate a polymerization model of the ESCRT-III complex.
Keywords : CHMP Polymers ESCRT
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Aurélien Dordor. Etude du mécanisme de polymérisation des protéines du complexe ESCRT-III. Biologie structurale [q-bio.BM]. Université de Grenoble, 2012. Français. ⟨NNT : 2012GRENV047⟩. ⟨tel-01559085⟩

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