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Genomic, structural and functional characterization of odorant binding proteins in olfaction of mosquitoes involved in infectious disease transmission

Abstract : The role of odorant binding proteins in the olfaction of mosquitoes, the primary mechanism of human host recognition, has been an important focus of biological research in the field of infectious disease transmission by these insects. This thesis provides an in depth knowledge of these proteins in three mosquito species Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus. A large scale analysis on these genomes has been carried out towards the identification of the odorant binding proteins in the mosquito genomes. Identification of many new OBP members, in particular in the Aedes aegypti and Culex quinquefasciatus species, and an extensive phylogenetic analysis presenting a novel classification of the OBP subfamilies of these mosquito species has been proposed. This results further demonstrates the extraordinary multiplicity and diversity of the OBP gene repertoire in these three mosquito genomes and highlights the striking sequence features that are nevertheless highly conserved across all mosquito OBPs. Owing to the availability of homologous structures from mosquitoes or related species, the 3D structure modelling of all the Classic OBPs from the three genomes (representing in total 137 structures) has been performed. This was completed by large scale docking studies on these structures by screening a large set of compounds that are known to be mosquito attractants or repellents. These provide many exciting new insights into the structural and functional aspects towards understanding the efficacy of some repellents and of some attractants from human emanations. Through molecular dynamics simulation, the structural changes observed in an OBP bounded to an odorant when pH conditions are modified were characterized and the probable mechanism of ligand binding and release is presented. This work provides the first insights to many of the long awaited questions on the genomic, structural and functional characterization of mosquito OBPs and can be viewed as a reliable starting point for further experimental research focussed on these aspects.
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  • HAL Id : tel-00979587, version 1

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Malini Manoharan. Genomic, structural and functional characterization of odorant binding proteins in olfaction of mosquitoes involved in infectious disease transmission. Agricultural sciences. Université de la Réunion, 2011. English. ⟨NNT : 2011LARE0022⟩. ⟨tel-00979587⟩

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