Theories and predictions of models describing sequential interactions between the receptor, the GTP regulatory unit, and the catalytic unit of hormone dependent adenylate cyclases

In this study we have examined the possible modes of interaction between the three functional units of hormone dependent adenylate cyclase: the hormone-receptor complex R, the nucleotide binding protein N, and the catalytic moiety C. Five models were considered: Model 1, N precoupled to C; Model 2, N interacts with C, only NC interacts with R; Model 3, N shuttle model, ternary complex activation (inactive N associates with R and activated N' associates with C); Model 4, restricted ternary 'N shuttle' model; (inactive N is coupled to R and active N' is coupled exclusively to C); Model 5, the binary complex N shuttle model (activation of N occurs at the binary complex RN and activated N' then dissociates from R and binds to C activating the latter). In all the models we have not allowed the complex RNC or RN to accumulate, since the receptor was assumed to act catalytically. This assumption is based on experimental findings in the turkey erythrocyte system. In each model we examine the overall kinetics of activation and the dependence of the rate on concentration of receptor N unit and the C unit within the membrane. We then compare the predicted kinetic features of each model with the experimental results obtained for turkey erythrocytes.