What is the Difference Between Heteromeric G Protein and Monomeric G Protein

The key difference between heteromeric G protein and monomeric G protein is that heteromeric G protein is a large membrane-associated G protein made up of alpha (α), beta (β), and gamma (γ) subunits, while monomeric G protein is a small membrane-associated G protein made up of only an alpha subunit.

G proteins (guanine nucleotide-binding proteins) are a family of proteins that act as molecular switches inside the cells. They are involved in transmitting signals from a variety of stimuli outside a cell to the interior. G proteins can be classified into two distinct families of protein: heteromeric G protein and monomeric G protein. Heteromeric G protein is a large protein, while monomeric G protein is a small protein.

CONTENTS

1. Overview and Key Difference
2. What is Heteromeric G Protein
3. What is Monomeric G Protein
4. Similarities – Heteromeric G Protein and Monomeric G Protein
5. Heteromeric G Protein vs Monomeric G Protein in Tabular Form
6. Summary – Heteromeric G Protein vs Monomeric G Protein

What is Heteromeric G Protein?

Heteromeric G protein is a large G protein that is made up of alpha (α), beta (β), and gamma (γ) subunits. Heteromeric G protein forms a heterotrimeric complex. The biggest non-structural difference between heterotrimeric and monomeric G protein is that heterotrimeric G protein binds to its cell surface receptor (G protein-coupled receptors) directly. The alpha subunit of heteromeric G protein is usually attached to either a GTP or GDP that serves as an on or off switch for the activation of G protein.

When ligands bind to a GPCR, the GPCR acquires GEF (guanine nucleotide exchange factor) ability. This activates the G protein by exchanging the GDP on the alpha subunit to GTP. The binding of GTP to the alpha subunit results in a structural change and dissociation of the alpha subunit from the rest of the G protein. Generally, the alpha subunit binds membrane-bound effector proteins for the downstream signalling cascade. The beta-gamma complex can also carry out this function. Furthermore, heteromeric G proteins are involved in pathways such as the cAMP/PKA pathway, ion channels, MAPK, and PI3K.

What is Monomeric G Protein?

Monomeric G protein is a small membrane-associated G protein that is made up of only an alpha subunit. The small monomeric G protein is homologous to the alpha subunit of the large heteromeric G protein. This family of small GTPases includes the RAS superfamily, which is further split into subfamilies based on structural, sequence, and functional similarities. Moreover, each subfamily of small GTPases plays a slightly different role vital in the regulation of intracellular signalling pathways.

Like the alpha subunit of large heteromeric G protein, small monomeric G protein alternate between an on state (bound to GTP) and an off state (bound to GDP). Therefore, monomeric G proteins function as binary switches that regulate cytosolic signalling pathways. The above GDP/GTP cycling is controlled by two types of regulatory proteins associated with monomeric G proteins. Guanine exchange factors (GEFs) promote the formation of active or GTP bound form of monomeric G protein (RAS protein), while GTPase activating proteins (GAPs) accelerate GTPase activity and promote the inactive or GDP bound form of monomeric G protein (RAS protein)

What are the Similarities Between Heteromeric G Protein and Monomeric G Protein?

• Heteromeric G protein and monomeric G protein are the two types of G proteins.
• The alpha subunit of heteromeric G protein is structurally related to the monomeric G protein.
• Both proteins bind to GTP and hydrolyze it to GDP, thereby acting as molecular switches.
• The rate of GTP hydrolysis catalyzed by both proteins can be increased by GAP proteins.
• They are tethered to the internal surface of the plasma membrane by means of post-translational lipid modifications.

What is the Difference Between Heteromeric G Protein and Monomeric G Protein?

Heteromeric G protein is a large membrane-associated G protein made up of alpha (α), beta (β), and gamma (γ) subunits, while monomeric G protein is a small membrane-associated G protein made up of only the alpha subunit. Thus, this is the key difference between heteromeric G protein and monomeric G protein. Furthermore, heterotrimeric G protein binds to its cell surface receptor (G protein-coupled receptors) directly. On the other hand, monomeric G protein binds to its cell surface receptor (G protein-coupled receptors) indirectly.

The below infographic presents the differences between heteromeric G protein and monomeric G protein in tabular form for side by side comparison.

Summary – Heteromeric G Protein vs Monomeric G Protein

G proteins are a family of proteins that act as molecular switches inside the cells. Heteromeric G protein and monomeric G protein are the two types of G proteins. Heteromeric G protein is a large membrane-associated G protein comprised of alpha (α), beta (β), and gamma (γ) subunits. Monomeric G protein is a small membrane-associated G protein comprised only of an alpha subunit. So, this summarizes the difference between heteromeric G protein and monomeric G protein.

Reference:

1. “Heterotrimeric G Protein.” An Overview | ScienceDirect Topics.
2.“Monomeric Guanine Nucleotide Binding Protein.” An Overview | ScienceDirect Topics.

Image Courtesy:

1. “GPCR cycle” By Repapetilto – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Ras-like g-protein” By A08821156 – Own work (CC BY-SA 3.0) via Commons Wikimedia