Nucleotide Exchange Reactions and G Protein Activation

Any model or theory is valid only as long as it explains all experimental observations. A new or adapted model for G protein activation should thus be introduced only when there are particular experimental findings that do not correspond with the established theory. Furthermore, this new model must account for all findings which can also be explained by the currently widely accepted exchange theory, including data concerning nucleotide exchange reactions which are outlined below. These current models (e.g., Fig 5.1) assume GTP binding to HR*G or R*G to occur immediately after pre-bound GDP release. Since the release of pre-bound GDP from the G protein is thought to be the rate limiting step in the activation process, the role of the agonist and R* is suggested to be a catalytic one, increasing the rate of GDP dissociation.