Opioid receptor random mutagenesis reveals a mechanism for G protein-coupled receptor activation.

The high resolution structure of rhodopsin has greatly enhanced current understanding of G protein-coupled receptor (GPCR) structure in the off-state, but the activation process remains to be clarified. We investigated molecular mechanisms of delta-opioid receptor activation without a preconceived structural hypothesis. Using random mutagenesis of the entire receptor, we identified 30 activating point mutations.

A naive Bayes model to predict coupling between seven transmembrane domain receptors and G-proteins.

Motivation: An understanding of the coupling between a G-protein coupled receptor (GPCR) and a specific class of heterotrimeric GTP-binding proteins (G-proteins) is vital for further comprehending the function of the receptor within a cell. However, predicting G-protein coupling based on the amino acid sequence of a receptor has been a daunting task. While experimental data for G-protein coupling exist, published models that rely on sequence based prediction are few.