Receptor-Bound Conformation of α-Peptide of Transducin (G_t) is not Stabilized by a “π-Cation” Interaction but by Constrained Lactam Bridges Between Residues 341 and 350

Abstract

Light-induced activation of rhodopsin (R*) leads to its conformation change and the binding of transducin G_t. Synthetic G_tα (340–350) peptide has been demonstrated to stabilize R* as does G_t. The bound conformation of R*-bound G_tα (340–350) has been determined by TrNOE NMR measurements [1]. The adjacent disposition of the 8-amino group of Lys-341 toward the side-chain phenyl ring of Phe-350 suggests a possible π-cation interaction. To investigate this π-cation hypothesis, we measured the affinity with R* of a series of α-peptide analogs with different para-substituents on the Phe-350 phenyl ring. In order to further exploit the proximity between the side chains of Lys-341 and Phe-350, we also prepared a-peptide analogs with straightforward lactam bridges between the side chains at 341 and 350.