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

TRANSDUCIN alpha subunit (alpha(t1)) shows extraordinarily high affinity to G protein beta gamma complex. One of the beta gamma-binding regions on alp ha(t1) is the amino-terminal helix. Alanine-23 is uniquely found on alpha(t 1) 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 s timulation of type II adenylyl cyclase. The functional impairment is indepe ndent to the protein expression levels. Molecular modeling indicated that t he hydrophobic interaction between the side chains of alanine-23 of alpha(t 1) and leucine-55 of the beta(1) subunit could be disrupted by the introduc tion 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. Neu roReport 10:1993-1996 (C) 1999 Lippincott Williams & Wilkins.