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Etude structurale des cassures d'hélices et son application à la modélisation des récepteurs couplés aux protéines G (RCPG)

Abstract : Our receptors of interest, the angiotensin receptors AT1 and AT2, belong to the family of class A G protein coupled receptors (GPCR). Up to very recently, bovine rhodopsin has been the only GPCR whose crystal structure was resolved. This structure is widely used as template for homology modelling of class A GPCR. The structure of rhodopsin consists of a bundle of seven transmembrane helices, common to all GPCRs. Most of these helices are not straight, but kinked or bent. For a bette understanding of the structural motifs related to kinked helices, we analyzed the properties of helix-Xhelix motifs in which two a-helices are linked by a single residue in a home-built structural database of HXH motifs. The linker residue can be classified in six distincts motifs. One of these motifs corresponds to p bulge. This GG motif, located at positions 2.56-2.57, is not conserved among GPCRs, but a proline is frequently observed in this helix, either at positions 2.58, 2.59 or 2.60. The receptors AT1 and AT2 possess a proline at position 2.58. The analysis of the evolution of the TMH2 proline positioning within the GPCR family strongly suggests that proline at position 2.58 corresponds to the deletion of one residue in the bulge elbow. This assumption is corroborated by 3D data mining of the Protein data bank. These results indicate that the rhodopsin structure ca be directly used as a template to modelTMH2 when proline is located at position 2.59 or 2.60. When proline is located at position 2.58, the rhodopsin structure can also be used, but the deletion of one residue in the elbow is taken into account. In that case, the helix bulge of rhodopsin can be mimicked by a typical ?proline? kink.
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Submitted on : Friday, December 12, 2008 - 6:24:19 PM
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  • HAL Id : tel-00346950, version 1

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Julie Devillé. Etude structurale des cassures d'hélices et son application à la modélisation des récepteurs couplés aux protéines G (RCPG). Modélisation et simulation. Université d'Angers, 2007. Français. ⟨tel-00346950⟩

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