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C terminus of cognate G protein stabilizes GPCR conformational flexibility, allowing tighter binding to G protein, deeper insertion of C terminus in receptor interface. Agonist-stimulated GPCRs are able to interact with different G proteins; however, the cognate G protein binds deeper into the receptor based on favorable interactions between the Gα C terminus and the GPCR, whereas the non-cognate interaction is hindered by unfavorable interactions between Gα C terminus and GPCR.
