Alanine-23 of transducin alpha subunit is involved in defining the affinity for betagammma complex.

Transducin alpha subunit (alpha(t)1) shows extraordinarily high affinity to G protein betagamma complex. One of the betagamma-binding regions on alphat1 is the amino-terminal helix. Alanine-23 is uniquely found on alphat1 but not other members of the Gi-subfamily. Mutation of alanine-23 into serine reduced the ability of alpha(t)1 to sequester betagamma-mediated stimulation of type II adenylyl cyclase. The functional impairment is independent to the protein expression levels. Molecular modeling indicated that the hydrophobic interaction between the side chains of alanine-23 of alpha(t)1 and leucine-55 of the beta1 subunit could be disrupted by the introduction of a hydroxyl group. This study showed that alanine-23 of alpha(t)1 is probably involved in defining its affinity for the betagamma complex.