The GTPase Superfamily General Functions and Mechanism

Proteins of the GTPase superfamily are found in all plant, bacterial and animal systems. The following examples illustrate the central functions of the regulatory GTPases in the cell. 

The members of the GTPase superfamily show an extensively conserved reaction mechanism. A common trait is a switching function that enables a reaction chain to be switched on or off (review Bourne et al., 1990). 

The GTPases bring about the transition between the active and inactive states in a cyclic process that can only run in one direction, due to the irreversible hydrolysis of GTP. 

At least three different GTPase states can be differentiated in the GTPase cycle the active GTP form, the inactive GDP form and an empty form of the GTPase, which is generally a short-lived state. 

The switch function of the GTPase is based on the specific ability of the different functional states of the GTPase to interact with the proteins that precede and follow in the signal chain. A particular GTPase is characterized by the proteins with which the active and inactive forms interact. A special characteristic of the active GTP form is that it may activate effector enzymes further on in the reaction chain, e.g., adenylyl cyclase, and thus actively transmits the signal. 

How effectively a signal can be transmitted by a GTPase depends on the relationship of the concentration of the active GTP form to the inactive GDP form. This, in turn, is determined by the relationship of the rate constant for the dissociation of GDP, kdiss.GDP to the rate constant of GTP hydrolysis, kcat,GTP  

This relationship is valid if it can be assumed that the GTP concentration is not limited and that GTP binds very rapidly to the empty form of the GTPase. A special characteristic of the regulatory GTPases is that both rate constants may be regulated by specific proteins. The proportion of GTPase that exists in the active form can be altered by at least three processes  

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