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La reconnaissance de la courbure membranaire par ArfGAP1

Abstract : The COPI coat drives the budding of small vesicle from Golgi apparatus. After being recruited by membrane-bound Arf1-GTP, the COPI coat subunits (Coatomer) polymerise, and shape mechanically the lipid membrane into a spherical structure. Then, GTP hydrolysis in Arf1 is required for the disassembly of the COPI coat, but this reaction must be finely tuned to permit coat disassembly only after vesicle formation. ArfGAP1 is a cytosolic protein that associates in dynamic manner with the Golgi apparatus, and controls the cycling of COPI coat on membranes by catalyzing GTP hydrolysis on Arf1. Results from our lab indicated that the activity of ArfGAP1 is highly sensitive to membrane curvature. Thus a negative feed-back loop was suggested, where COPI assembly drives membrane curvature, which in turn prepares the coat for disassembly by recruiting ArfGAP1, thereby promoting GTP hydrolysis in Arf1.
During my thesis, I found that two motifs in the central region of ArfGAP1 act as lipid-packing sensors and help anchor ArfGAP1 at the surface of highly curved membrane. These “ALPS” motifs, which are not structured in solution, adopt an amphipathic helical structure on curved membranes. These helices contrast from classical membrane-adsorbing helices in the abundance of serine and threonine residues and the paucity of charged residues in their polar faces. Because these residues cannot make electrostatic interaction with lipid polar heads, the adsorption of ALPS motifs is driven solely by the insertion of hydrophobic residues between lipids and is thus strongly favored by the creation of lipid packing defects such as those introduced by high membrane curvature.
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Submitted on : Wednesday, September 10, 2008 - 10:52:12 AM
Last modification on : Monday, October 12, 2020 - 10:27:24 AM
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  • HAL Id : tel-00320072, version 1



Bruno Mesmin. La reconnaissance de la courbure membranaire par ArfGAP1. Biochimie [q-bio.BM]. Université Nice Sophia Antipolis, 2007. Français. ⟨tel-00320072⟩



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