Rhodopsin–transducin coupling: Role of the Gα C-terminus in nucleotide exchange catalysis

In the early steps of visual signal transduction, light-activated rhodopsin (R*) catalyzes GDP/GTP exchange in the heterotrimeric G protein (Gαβγ) transducin. We recently reported that the catalytic interaction involves two sequential steps. An initial docking between R* and Gβγ leads to conformational changes which make the C-terminus of Gα (CTα) available for binding to R*. Binding of CTα by R* then triggers GDP/GTP exchange in the Gα subunit. To further study this two-step mechanism, we investigated different single amino acid substitutions within CTα and discuss the effects of high affinity mutations on nucleotide exchange catalysis.