Mutagenese und funktionelle Charakterisierung des humanen CCR3-Rezeptors


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BRASSEIT, Jennifer, 2008. Mutagenese und funktionelle Charakterisierung des humanen CCR3-Rezeptors

@mastersthesis{Brasseit2008Mutag-6573, title={Mutagenese und funktionelle Charakterisierung des humanen CCR3-Rezeptors}, year={2008}, author={Brasseit, Jennifer} }

2011-03-24T17:27:31Z Brasseit, Jennifer application/pdf 2011-03-24T17:27:31Z deu Mutagenesis and functional Characterization of the human CCR3 Receptor Mutagenese und funktionelle Charakterisierung des humanen CCR3-Rezeptors Brasseit, Jennifer 2008 Asthma is a chronic-inflammatory disease of the airways and about 15% of the population in the industrialized countries suffer from it. The characteristic inflammation of the lung is, amongst others, caused by eosinophilic granulozytes which get activated via chemotactic receptor 3 (CCR3). In order to stop activation of eosinophils and the following inflammation and destruction of the lung tissue, research aims to develop specific receptor antagonists. This turns CCR3 into an interesting and promising therapeutic target. To better understand the interaction of receptor and ligands a receptor model was established which should be verified experimentally. Eight specific amino acids (AA) which are located in the transmembranal region (TMR) of CCR3 were mutated and CHO-cells were transfected with them. The influence of the mutations on ligand-receptor interaction were investigated using an receptor internalisation assay. The data obtained clearly demonstrate that some AA (Y113, H114, Y291) have strong influence on the interaction of ligands with CCR3. For other AA (R95, Y41) it could be shown that they either decrease or even increase interaction of different ligands. Both could be demonstrated for natural ligands as well as agonistic and antagonistic small molecules. This was very surprising as up to now it is believed that natural ligands only interact with the N-terminal region of the receptor, but not with the TMR.<br />Based on the data obtained some of the investigated AA are clearly involved in ligand-receptor interaction and/or signal transduction. Comparisons to similar GPCR studies also suggest an impairment of binding of the ligands and therefore overlapping interaction sides of natural ligands and small molecules. deposit-license

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