Kelley Lab at UMaine

G-proteins: On/off Switches of the Cell

G-proteins are cellular on/off switches.  Much like there are many different types of on/off switches in your house, living room light switches, kitchen light switches, fan switches, refrigerator switches, or stove switches, there are many different types of G-proteins, controlling a huge variety of cellular processes, but each one works fundamentally the same way.

When bound to the nucleotide GDP, G-proteins are generally in the “Off” position.  They are turned on by proteins called Guanine nucleotide Exchange Factors (GEFs) that cause the G-protein to let go of GDP, and pick up a GTP.  When bound to the nucleotide GTP, G-proteins are generally in the “on” position.  In this configuration, they are capable of interacting with their effector proteins and signaling.

Small G-proteins are members of the Ras superfamily of small GTPases.  They are also referred to as monomeric G-proteins, as they, wait for it…. exist as monomers.

Large G-proteins are also called heterotrimeric G-proteins, because they consist of three subunits, Gα, Gβ, and Gγ.  Gα is the subunit most like small G-proteins, it will bind to GDP and GTP.  When it is bound to GTP, the Gα will release the Gβ/Gγ dimer.  Free Gα and free Gβ/Gγ are then able to bind effectors and initiate signaling.