logo_sm.gif (1977 bytes)The Ras Protein, A Molecular Switch


The ras protein belongs to a large super-family of proteins known as "low-molecular weight G-proteins". These proteins are called "G-proteins" because they bind guanine nucleotides (GTP and GDP).  They are called "low-molecular weight" to distinguish them from another, distinct, clan of guanine nucleotide-binding proteins, the heterotrimeric G-proteins.

Here is a model of the ras protein with an analog of GTP bound to it:

 

GTP (on/off toggle) 

Protein Model

(in light blue)

(colored by 2o structure: alpha helix, beta sheet, beta turns and random coils)

   

Ras acts as a switch. In it's resting (or "off") state it is found complexed with GDP. In it's active (or "on") state it is has a molecule of GTP bound to it. Ras is turned "on" by removing the GDP and replacing it with a GTP. This nucleotide exchange reaction is controlled and catalyzed by proteins called "exchange factors".

Ras possesses a GTPase activity that converts  GTP to GDP  by hydrolyzing the gamma phosphate off the GTP. Thus the ras protein has the ability to return to "off" state automatically. This reaction is also regulated by other proteins, called GTPase activating proteins or "GAPs".

ras_switch.gif (1322 bytes)

Both the exchange factors and GAPs are regulated by processes "upstream" of ras that ultimately begin at the level of receptors in the cell membrane. The result of this regulation is that when cells are stimulated there is an increase in the cellular level of the rasGTP complex.

Likewise, the active rasGTP complex binds to one or more "effector" molecules. This binding results on the signal being passed to "downstream" molecules and ultimately to transcription factors that alter the patterns of RNA expression in the nucleus.

In other words, the ras protein functions within a signal transducing cascade of reactions. The level of signal passing through ras depends on the "balance" between the amounts of rasGTP and rasGDP complex present in a cell. Events that tip the balance towards rasGDP will inhibit downstream events. Conversely, events that tip the balance towards rasGTP will activate downstream events.

balance.gif (1900 bytes)

Copyright 2000, 2007 F.R. Gorga Last update:
09-Mar-2007