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Residue conservation and dimer-interface analysis of olfactory receptor molecular models

机译:嗅觉受体分子模型的残基保守和二聚体界面分析

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Olfactory Receptors (ORs) are members of the Class A rhodopsin like G-protein coupled receptors (GPCRs) which are the initial players in the signal transduction cascade, leading to the generation of nerve impulses transmitted to the brain and resulting in the detection of odorant molecules. Despite the accumulation of thousands of olfactory receptor sequences, no crystal structures of ORs are known tο date. However, the recent availability of crystallographic models of a few GPCRs allows us to generate homology models of ORs and analyze their amino acid patterns, as there is a huge diversity in OR sequences. In this study, we have generated three-dimensional models of 100 representative ORs from Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans and Sacharomyces cerevisiae which were selected on the basis of a composite classification scheme and phylogenetic analysis. The crystal structure of bovine rhodopsin was used as a template and it was found that the full-length models have more than 90% of their residues in allowed regions of the Ramachandran plot. The structures were further used for analysis of conserved residues in the transmembrane and extracellular loop regions in order to identify functionally important residues. Several ORs are known to be functional as dimers and hence dimer interfaces were predicted for OR models to analyse their oligomeric functional state.
机译:嗅觉受体(OR)是类视紫红质的G蛋白偶联受体(GPCR)的成员,它们是信号转导级联反应的最初参与者,导致生成传递到大脑的神经冲动并导致检测到气味分子。尽管积累了成千上万的嗅觉受体序列,但迄今为止尚无OR的晶体结构。但是,由于一些OR序列的多样性很大,因此最近一些GPCR的晶体学模型的可用性使我们能够生成OR的同源性模型并分析其氨基酸模式。在这项研究中,我们已经生成了来自智人,小家鼠,果蝇,秀丽隐杆线虫和酿酒酵母的100个代表性OR的三维模型,这些模型是在综合分类方案和系统发育分析的基础上选择的。以牛视紫红质的晶体结构为模板,发现全长模型在Ramachandran图的允许区域中有90%以上的残基。该结构进一步用于分析跨膜和细胞外环区域中的保守残基,以鉴定功能上重要的残基。已知几个OR可以用作二聚体,因此可以预测OR模型的二聚体界面以分析其寡聚功能状态。

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