Core Concepts
In this article, you will learn about the G protein coupled receptor, the structure of G proteins, the basic mechanism of G protein signaling, and several examples of G protein signaling pathways.
Topics Covered in Other Articles
- Proteins and Amino Acids
- Catalysts
- Protein Folding
- Hormones
- Plasma Membrane
- Metabolic Pathways
G Protein Coupled Receptor Signaling
The G protein signaling pathway is a common way the cells of organisms communicate with one another. Messages between cells come in the form of chemicals, which release from source cells and bind to the receptors on the membranes of target cells.
In G protein signaling, after a chemical signal binds to a receptor, that receptor activates structures called G proteins. Next, these G proteins carry the message forward by interacting with another membrane protein. Then, this protein releases secondary messenger molecules, which carry the message further to initiate the cell’s response.
G Protein Coupled Receptor Signaling Components
The G protein signaling pathway has three basic protein components:
- G Protein Coupled Receptor
- G Protein
- Membrane Enzyme
The G protein coupled receptor proteins cross the entire plasma membrane, with parts that touch both inside and outside the cell. The receptor’s intracellular portion binds with G proteins, which themselves anchor to phospholipids on the cell’s inside.
When inactive, G proteins bind to guanosine diphosphate (GDP), an energy storage molecule similar to ATP. However, GDP is relatively energy poor compared to guanosine triphosphate (GTP), which replaces GDP to activate the G protein. Accordingly, the “G” in G protein refers to this important interaction between GDP and GTP.
The membrane enzyme involved in this pathway is located near the receptor and G proteins. Crucially, this enzyme catalyzes the production of secondary messenger molecules that carry the chemical message forward.
G Protein Structure
Since G protein signaling is used by a wide diversity of species for numerous functions, the structure of G proteins can vary considerably. However, each G protein forms a trimer, meaning that they have three polypeptide subunits: the alpha, beta, and gamma subunits. Different genes code for each subunit, and the polypeptides are only connected to one another during protein folding.
Similar to most other proteins, each G protein subunit has different function and activity. The alpha subunit binds to GDP and GTP and is responsible for G protein activation. Contrastingly, the beta and gamma subunits bind to the phospholipid anchor of the molecule, and play no role in activation. Interestingly, some G protein signaling pathways in metabolism and neural signaling involve the separation of the alpha subunit from the beta and gamma subunits. Then, the two separate pieces of protein both activate enzymes which separately produce secondary messengers.
G Protein Coupled Receptor Signaling Outline
G protein signaling follows a simple procedure that passes the chemical signal between each protein component.
First, a chemical signal from outside the cell binds to the receptor. This shifts the protein structure of the receptor, which allows GTP to replace GDP on the G protein alpha subunit. Consequently, the binding of GTP activates the G protein, which is released from the receptor.
Second, the phospholipid anchors of the G protein freely diffuse in the plasma membrane. Eventually, the activated G protein binds to the cell enzyme located nearby.
Third, the binding of G protein results in the enzyme producing secondary messenger molecules. Finally, these molecules carry forward the original chemical signal, which eventually triggers the desired cell response.
G Protein Coupled Receptor Signaling Examples
The G protein signaling pathway is a crucial piece of cellular communication, and this pathway is present in many different body systems in humans. In fact, many researchers estimate that as high as a third of all pharmaceutical drugs target this pathway to induce or block certain biological effects.
Let’s look at a few examples of G protein signaling pathways in the human body:
- Reproductive Development
- Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) signal the development of human reproductive systems by activating G protein coupled receptors. These pathways use cyclic adenosine monophosphate (cAMP) as a secondary messenger.
- Calcium Regulation
- Parathyroid Hormone (PTH) and Calcitonin interact with bone tissue cells through G protein signaling. Specifically, PTH signals the breakdown and release of calcium from bones into the bloodstream, while Calcitonin signals the uptake of calcium. These pathways also utilize cAMP as a secondary messenger.
- Smell (Olfaction)
- Odorant molecules activate olfactory neurons through G protein signaling, which is how organisms can smell. These pathways also utilize cAMP as a secondary messenger.
- Blood Pressure Regulation
- Vasopressin (also known as Antidiuretic Hormone or ADH) activates cells in blood vessels to constrict, raising blood pressure, through G protein signaling. This pathway uses inositol triphosphate (IP3) and diacylglycerol (DAG) as secondary messengers.
- Heart Rate Regulation
- Acetylcholine slows the heart rate by interacting with G coupled receptor proteins in the heart. This pathway involves the alpha subunit separating from the beta and gamma subunits of the G protein to independently activate secondary messenger producing enzymes.