Signal transduction of Olfactory Receptors to thei.. (SIGT-OR-G)
Signal transduction of Olfactory Receptors to their G protein
Start date: Apr 1, 2013,
End date: Sep 30, 2014
G protein coupled receptors form the largest and most important class of cell surface receptors with a seven transmembrane fold. These proteins mediate diverse cell responses as reaction to input signals like hormones, peptides, light and endogenous ligands. Due to their central role, most drugs on the market target these receptors.In 2011 and 2012 incredible advance has been published in terms of X-ray structural data on GPCRs. Nevertheless, the actual mode of action and structural rearrangements remain poorly understood. Here the field of olfaction is lagging behind even more with few examples of purified receptors and no structural data.This project proposes to characterize the interaction of an Olfactory Receptor (OR) to its G protein Gaolf from the Gas family. As basis a structural model of the OR will be evaluated by Cys scanning to identify the crucial interaction region of ILC2. In parallel the G protein will be crystalized to enable co-crystallization experiments with loop fragments. Based on these information peptides resembling ICL2 will be generated and examined for their ability to activate the G protein by fluorescent GTP analogs. The peptide will be kept in a loop-like conformation by a chemical, bivalent molecule. In a final step an azo compound will be incorporated in this molecule enabling to change the length in a light dependent manner to exert control over G protein activation by light.
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