Mechanisms of small CTP-binding proteins activation by their exchange factors

GTP-binding proteins are molecular switches that control multiple aspects o f cellular life and signal transduction. These molecules alternative betwee n an inactive, GDP-bound form and an active, GTP-bound form, and their acti vation is controlled by << exchange factors >>. The structures of several e xchange factors and their complexes formed with target small G proteins pro vide a better understanding of the mechanisms inducing the release of GDP a nd its subsequence replacement by GTP. The flexibility of two << switch >> regions is essential during the exchange process and the understanding of t he mechanism of inhibition of one of these exchange factors by the drug Bre feldin A suggests that the rearrangements that occur in these switch region s might represent the << Achille's heel >> by which new drugs might inhibit some of these exchange factors.