What is a Ligand?

A complicated signaling route inside a cell starts with a single critical event: binding a signaling molecule, or ligand, to its receiving molecule or receptor. To understand these complex biochemical processes, it is imperative first to understand their participants.

A ligand is any molecule or atom that binds reversibly to its target receptor. A solitary atom or ion can serve as a ligand. However, it may also comprise a more complex molecule of several atoms. A ligand may be an organic or inorganic molecule found in nature.

Although ligands form the most fundamental component of many complex biochemical processes, they are intricate in their own right. Understanding how ligands bind to their target receptors and how this contributes to their classification is vital in grasping the fundamental concepts of biochemistry.

What Is A Ligand?

According to the biochemical definition, a ligand is a compound that combines with a biomolecule, known as a receptor, to carry out a biological function—charge, hydrophobicity, and molecular structure influence the relationship between the ligand and its receptor target.

As ligands bind to their target receptors, they can dissociate to reverse their relationship. However, in biological systems, the bonding between a ligand and its receptor is less consistent than inorganic systems. This irregular binding pattern is of particular interest in drug design since synthetic molecules are modified to imitate natural ligands so that they can influence biological processes.

One of the ways in which we classify ligands is the magnitude of the physiological response they initiate as a result of their binding. A receptor agonist is a ligand that binds to and changes the receptor’s behavior, causing a physiological response. A full agonist is a ligand that produces the maximum possible response, while a partial agonist produces only a fraction.

Molecules that cause a complete lack of response when binding may also be classified as ligands. These molecules are known as receptor antagonists. Similarly, a partial antagonist reduces the physiological response, while a full antagonist completely diminishes all responses.

However, ligands that bind to cause the opposite response to the physiological norm are not classified as antagonists. These molecules are termed ‘inverse agonists’ because, although it is opposite to the usual response, they still solicit a reaction.

How Are Ligands Classified?

Ligands can be classified in several ways, with binding affinity being one of these ways – binding affinity describes how ligands interact with their receptors. Intermolecular forces bind these molecules together, including ionic bonds, hydrogen bonds, and van der Waals forces. Higher affinity forces include ionic bonds, whereas examples of weaker affinity bonds include van der Waals forces.

Higher attractive forces between the ligand and its receptor generally cause higher affinity ligand binding. This enhanced ligand binding allows a small ligand concentration to occupy a significant fraction of the receptor pool. This phenomenon suggests that only a small ligand concentration is needed to produce the maximal response.

However, lower attractive forces lead to lower affinity ligand binding and require higher ligand concentrations to produce a physiological response. Despite this pattern in receptor binding, there is no correlation between the duration of receptor pool occupancy and the lifespan of the receptor-ligand complex.

Therefore, the magnitude of the physiological response induced and the concentration of the agonist needed to trigger this response describe an agonist’s binding to a receptor. This response is often measured as the effective concentration, shortened to ‘EC50’, which is the concentration required to produce the half-maximal response.

High-affinity binding of ligands to receptors is physiologically relevant when the binding energy may be utilized to create conformational changes in the receptor. When this type of binding occurs, it results in changed physiological behavior.

For example, when a ligand binds to receptor sites on channels in the cell membrane, it can trigger conformational changes in the membrane channel and influence molecules’ movement across the membrane.

Ligands may also be classified according to their selectivity for their receptor targets. While non-selective ligands bind to various receptor types, selective ligands tend to bind to a relatively small number of receptor types.

This is an essential differentiation in drug design since non-selective medications tend to have more negative side effects because they bind to other receptors in addition to the one responsible for the intended effect.

Similarly, ligands can be classified according to how many receptors they can bind. For example, protein ligands can be classified according to how many protein chains they bind. “Polydesmic” ligands are common in protein complexes and are ligands that bind more than one protein chain. “Monodesmic” ligands are ligands that bind a single protein chain.

Another classification for ligands is centered around their structure. An inert linker can join two ligands to form bivalent ligands. Bivalent ligands can be of many different types and are frequently categorized according to their target receptors.

This categorization leads to an extension of the classification of ligands according to their receptor binding. Homobivalent ligands target two similar receptor types, while two different receptor types are bound to heterobivalent ligands. Similarly, bitopic ligands target orthosteric and allosteric binding sites on the same receptor.

Examples Of Ligands In The Body

Because of its abundance in everyday life, oxygen is frequently overlooked as an example of a ligand. Living organisms require oxygen to reach all their mitochondria in the circulation and bodily tissues to fuel biochemical processes. However, fulfilling this requirement is no simple feat. Oxygen can only flow through a few cell layers of tissue to diffuse to the cells.

Because oxygen cannot independently move through the body, all organisms over a specific size require a circulatory system. Even yet, getting the oxygen ligand to the right place is challenging. Specialized proteins are used to overcome this challenge.

Hemoglobin is the main blood protein in charge of carrying oxygen in mammals. The heme ligand, which has an iron atom and can aid in binding oxygen, is the first thing to which the hemoglobin protein binds. As a result, hemoglobin absorbs oxygen from the lungs.

The blood’s carbon dioxide level grows as heme moves to the body. The pH falls as a result, and hemoglobin’s structure alters. As a result, the ligand, oxygen, is compelled to be released and may be taken up by the cells that require it. The release of oxygen into the blood restores the circulation’s pH level.

Carbon monoxide is one of oxygen’s principal rivals. This competition exists because carbon monoxide and oxygen have a strong affinity for hemoglobin. In other words, carbon monoxide won’t dissociate from hemoglobin after it has bonded to it.

As a result, someone exposed to high carbon monoxide levels quickly has all their hemoglobin saturated with the incorrect ligand. Their body won’t be able to deliver oxygen to the brain and other tissues. The inability to carry the oxygen means that even after receiving oxygen, the individual may still suffocate.

Another example of a ligand commonly found in the body is dopamine. The brain releases dopamine as an indication of joy following achievement. Dopamine, therefore, is associated with the experience of motivation.

When the brain produces the ligand dopamine, the dopamine receptors in your brain become active. Following this activation, your brain experiences a sense of accomplishment. Drugs like cocaine and methamphetamine can readily disrupt this universal reward center.

Instead of directly competing with the ligand, some stimulants enhance dopamine’s efficacy. By restricting the quantity of dopamine that may be recycled, the dopamine remains in the synapse, and the brain continues to feel “rewarded” constantly.

This is a risky emotion that may quickly result in drug addiction. Even though drugs are dangerous, your brain’s sensations and the additional dopamine encourage you to use the substance more frequently.

How Are Ligands Involved In Cell Signaling?

Chemical signals are frequently used by cells to communicate. These chemical signals, proteins, or other compounds produced by the transmitting cell and released into the extracellular space, are secreted by the cell.

A neighboring cell must have the proper receptor for a signal to detect it. When a signaling molecule attaches to its receptor, it modifies the receptor’s structure or function and causes a change inside the cell. As a collective noun for chemicals that bind to other molecules, such as receptors, signaling molecules are referred to as ligands.

A ligand sends the message inside the cell through a series of chemical messengers. Ultimately, it causes a change in the cell, such as a change in a gene’s activity or even the triggering of an entire process, like cell division. The initial intercellular signal changes into an intracellular signal that causes a reaction.

However, not all cell pairs exchange signals in the same way, and not all transmitting and receiving cells are closely neighboring. Multicellular organisms use four types of signaling to communicate with one another: paracrine, autocrine, endocrine, and direct touch. The distance a signal must travel through an organism to reach its target cell is the critical distinction between the various types of signaling.

Nearby cells often communicate with one another by releasing chemical messengers. These messengers are ligands that can diffuse through the space between the cells. Paracrine signaling is the term for this kind of communication, in which cells communicate with one another over comparatively short distances.

Cells can locally coordinate their activity with neighboring cells thanks to paracrine signaling. Despite being employed in a wide range of tissues, paracrine signals play a crucial role in development because they enable one group of cells to instruct a nearby group of cells on which cellular identity to adopt.

Synaptic signaling, the transmission of signals by nerve cells, is one distinctive instance of paracrine signaling. The synapse, the intersection between two nerve cells where signal transmission occurs, inspired the naming of this procedure.

When the transmitting neuron fires, an electrical impulse travels down a long, fiber-like extension known as an axon and goes quickly through the cell. The release of chemicals known as neurotransmitters, which swiftly bridge the tiny space between the nerve cells, is triggered when the impulse reaches the synapse.

The neurotransmitters attach to receptors as they reach the receiving cell, changing the cell’s internal chemistry. This binding frequently opens ion channels and modifies the electrical potential across the membrane.

When a cell signals to itself through autocrine signaling, it secretes a ligand that binds to receptors on its own surface. There are several mechanisms in which autocrine signaling is crucial. For instance, autocrine signaling is crucial for cell identity acquisition and reinforcement during development. Autocrine signaling is significant in cancer from a medical perspective and is believed to be crucial for metastasis.

The binding of a signal to the transmitting cell and other nearby cells comparable to it can frequently have both autocrine and paracrine effects.

In endocrine signaling, cells communicate over longer distances and frequently convey messages through the circulatory system to do so. Long-distance signaling uses hormones that are created by specialized cells and released into the circulation to reach target cells that are in different sections of the body.

The thyroid, the hypothalamus, and the pituitary, together with the gonads and the pancreas, are endocrine glands in humans that produce hormones. A variety of hormones, many of which are master regulators of physiology and development, are released by each endocrine gland.

Direct touch signaling utilizes small channels, or gap junctions, to directly link adjacent cells. Signaling chemicals known as intracellular mediators can diffuse between the two cells thanks to these water-filled channels. Large molecules like proteins and DNA cannot move through the channels without specific aid, while small molecules and ions can travel between cells.

The present condition of one cell is communicated to its neighbor through the transmission of signaling molecules. This communication enables many cells to react in unison to a signal that may have been received by only one of them.

Two cells may attach to one another in a different type of direct signaling if they have complementary proteins on their surfaces. A signal is transmitted when the proteins attach and alter the structure of one or both proteins. This type of communication is particularly crucial in the immune system, where immune cells employ cell-surface markers to distinguish between the body’s own cells and those infected by pathogens.

Conclusion

According to the biochemical definition, a ligand is a compound that combines with a biomolecule, known as a receptor, to carry out a biological function. Ligands can be classified according to binding affinity, receptor selectivity, structure, and how many receptors they can bind at once.

Ligands are an integral part of cell communication, known as cell signaling. This intercellular communication may be paracrine, autocrine, endocrine, or direct. An example of ligands involved in these signaling processes includes oxygen and dopamine.

References

https://en.wikipedia.org/wiki/Ligand

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355565/#:~:text=Ligand%20binding%20models%20are%20useful,the%20binding%20sites%20of%20receptors.&text=Ligand%20binding%20models%20are%20useful,binding%20sites%20and%20receptors%20simultaneously.

https://www.khanacademy.org/science/ap-biology/cell-communication-and-cell-cycle/signal-transduction/a/signal-perception

https://www.researchgate.net/figure/Examples-of-intracellular-ligand-receptor-targets-molecules-and-mechanisms_tbl1_236920362

Theodore T.

Theodore is a professional psychology educator with over 10 years of experience creating educational content on the internet. PracticalPsychology started as a helpful collection of psychological articles to help other students, which has expanded to a Youtube channel with over 2,000,000 subscribers and an online website with 500+ posts.