The complex of PPARalpha and PPARgamma with the dual specificity agonist AZ 242 highlights the conserved interactions required for receptor activation. Together with the NMR data, this suggests a general model for ligand activation in the PPAR family. A comparison of the ligand binding sites reveals a molecular explanation for subtype selectivity and provides a basis for rational drug design.

Transmembrane seven helix bundles form a large family of membrane inserted receptors and are responsible for a wide range of biological functions. Experimental data suggest that their overall structure is similar to bacteriorhodopsin. We describe here a new approach for the modeling of transmembrane seven helix bundles based on statistically derived environmental preference parameters combined with experimentally determined features of the receptors. The method was used to create a model for the human beta 2-adrenoreceptor. This model is physically plausible, is in reasonable agreement with experimental data and may be helpful in planning new receptor engineering experiments.

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G-protein-coupled receptors (GPCRs) form one of the largest superfamilies of membrane proteins. Obtaining high yields of GPCRs remains one of the major factors limiting a detailed understanding of their structure and function. Photoreceptor cells (PRCs) contain extensive stacks of specialized membranes where high levels of rhodopsins are naturally present, which makes them ideal for the overexpression of GPCRs. We have generated transgenic flies expressing a number of GPCRs in the PRCs. Drosophila melanogaster metabotropic glutamate receptor (DmGluRA) expressed by this novel strategy was purified to homogeneity, giving at least 3-fold higher yields than conventional baculovirus expression systems due to the higher membrane content of the PRCs. Pure DmGluRA was then reconstituted into liposomes of varying composition. Interestingly, glutamate binding was strictly dependent on the presence of ergosterol.