Conformational states of the opiod receptors

This Thesis elucidates the relationships between structure and function of opioid receptors. The mechanism of opioid receptor function could be better understood on the basis of the recent knowledge of their three-dimensional structure. In the first part of the Thesis, methods for membrane protein crystallization and X-ray structural analysis are reviewed with a special focus on in meso crystallization. Next, the three opioid receptor subtype crystal structures are described and analysed, starting with their general architecture and proceeding to the detailed description including the binding pocket for opioid ligands with the help of visualization with the PyMol software. In its third part, this Thesis re-examines the structure-function correlations predicted on the basis of site-directed mutagenesis (Décaillot F.M. et al, Nature Structural Biology 10, 629, 2003) in the light of now available crystal structure. This analysis is pointing to the potentially important contacts of aspartate D128, suggesting that ligand binding and receptor activation might involve changes in its interaction with tyrosine Y308