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

Transducin a subunit (alpha(t1)) shows extraordinarily high affinity to G protein beta(gamma) complex. One of the beta(gamma)-binding regions on alpha(t1) is the amino-terminal helix. Alanine-23 is uniquely found on alpha(t1) but not other members of the G(i)-subfamily. Mutation of alanine-23 into serine reduced the ability of alpha(t1) to sequester beta(gamma)-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(t1) 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(t1) is probably involved in defining its affinity for the beta(gamma) complex.