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Globular Proteins


Proteins are the most abundant molecules found in living organisms. They play structural as well as functional roles in the bodies of living organisms. As structural molecules, they are present in nuclear material, cell membrane, cytoskeleton, etc. They are present in every organelle and every cell of a living organism.

Almost all the functions of a cell are carried out by proteins. Enzymes, needed for any biochemical reaction to take place in a cell, are proteins in nature. Other functional molecules such as ion channels, transport molecules, hormones, contractile molecules, etc. all are made up of proteins.

Proteins are made up of hundreds to thousands of amino acids. The final shape of a protein molecule is determined by the arrangement of amino acids within it. On the basis of the final shape of a protein molecule, they are divided into two classes; fibrous proteins and globular proteins.

Structural proteins are fibrous in nature while most of the functional proteins have globular structures.

As the name indicates, globular proteins have a structure that resembles a ball or a globe. Various amino acid chains are folded to form a globular structure. Haemoglobin and Myoglobin are the two most important globular proteins found in the human body.

In this article, we will read about the structure of globular proteins, their properties as well as functions performed by them. We will study various examples of globular proteins with special emphasis on haemoglobin. So, keep reading!

Haemoglobin is an example of globular proteins


Globular proteins have a tertiary structure as guided by the primary arrangement of amino acids in the polypeptide chains. The polypeptide chains in globular proteins are arranged in the form of domains. These domains undergo folding to form a globular molecule.

The amino acids are arranged in such a way that the hydrophobic side chains are buried inside the core of domains while the hydrophilic side chains lie on the surface of the molecule.

The structure of domains, chemical interactions stabilizing them, and their folding into globular proteins is described below.


Domains are the fundamental functional units of globular polypeptides. It has been proven that proteins having more than 200 amino acids usually contain two or more domains. The folding of a polypeptide chain in a domain takes place independently of folding in other domains. Therefore, each domain is said to behave like a small globular protein that has its own compact independent structure.

Haemoglobin, a globular protein found in blood, consists of 2 domains.

Interaction Stabilizing Domains

Domains have a globular, compact structure that is guided by the interaction between the side chains of their component amino acids. Following four chemical interactions play an important role in this regard.

1. Disulfide Bonds

It is the covalent linkage between two cysteine amino acids. Each cysteine amino acid has a sulfhydryl (-SH) in its side chain. These sulfhydryl groups react to form a disulfide bond represented by -SS-. The new residue thus formed is called cysteine residue.

A disulfide bond can be formed between two cysteine residues that are separated by many amino acids but are brought close by the folding of the polypeptide chain. The two cysteine resides taking part in the formation of the disulfide bond may even be located on two different polypeptide chains as seen in immunoglobulins.

Disulfide bonds provide stability to the domains and prevent denaturation in the extracellular environment.

2. Hydrophobic Interactions

These interaction among the hydrophobic groups in the side chains of amino acids allow the hydrophobic amino acids to be buried in the core of globular proteins. This is the basic characteristic of globular proteins that allows them to be soluble in water.

3. Hydrogen Bonds

A hydrogen bond is a non-covalent bond formed between a hydrogen atom, covalently attached to a highly electronegative atom such as N, O, or F, and another electronegative atom. An example of a hydrogen bond is the interaction between -OH group and H in water.

Hydrogen bonds among the polar groups on the surface of proteins and the solvent molecules contribute to their solubility in an aqueous environment.

4. Ionic Interactions

These take place among the charged groups in the side chains of amino acids present on the surface of the protein. An example is an interaction between negatively charged carboxylate group in the side chain aspartate and positively charged amino group in the side chain of lysine amino acids.

Folding of Polypeptide Chains

This is the final step in the formation of domains which later interact to form globular proteins. As mentioned earlier, folding of a polypeptide chain in a domain does not depend on folding in another domain.

The folding of the polypeptide chain into the final shape is guided by the interactions among the side chains of component amino acids. In the first step, the hydrophobic groups come together releasing water and forming the core of the domain. This hydrophobic effect results in the formation of secondary structures.

Once the core is formed, additional interactions take place among the side chains of amino acids leading to the formation of a fully folded, functional protein.

Role of Chaperons

Chaperons are the specialized proteins that help in the process of folding polypeptide chains. They interact with the polypeptide chain at various stages during the process of folding. These proteins bind to the hydrophobic amino acids of a polypeptide chain and prevent its folding until the synthesis is completed. Some chaperons form a cage-like structure. Polypeptide chain that is to be folded enter the cage, binds to its core via hydrophobic interactions, folds and gets released.

The folded domains thus formed interact with each other via different types of bonds to form the final structure of a globular protein. To explain it further, an example of the haemoglobin molecule will be discussed later.


The important characteristic properties of globular proteins are mentioned below.


As evident by the above discussion, globular proteins have a spherical shape resembling a ball. It is due to the folding of amino acid chains onto themselves to form tertiary structures. The compact arrangement of amino acids within a molecule allows the rounded spherical shape of these proteins.


Globular proteins are highly soluble in an aqueous environment because of the structural arrangement of amino acids. As mentioned earlier, hydrophilic amino acids are present on the surface of globular proteins while the hydrophobic amino acids are buried inside. Interactions among the polar groups on the surface of proteins and the polar water molecules contribute to their increased solubility.

Because of their solubility, globular proteins are found in free form in the cytoplasm as well as extracellular environment such as extracellular fluid, blood, etc. Examples include enzymes, albumin, myoglobin, haemoglobin, immunoglobins, etc.

Amino acid Sequence

Globular proteins are found to have an irregular sequences of amino acids. The amino acids in the polypeptide chains of these proteins do not repeat themselves at regular intervals. This is opposite to fibrous proteins that have highly repetitive sequence of amino acids.

However, the amino acids sequence of globular proteins is highly specific. The number and the position of amino acids in two different molecules of a globular protein never varies. If, due to some mutation, the position of even one amino acid is changed, it severely affects the structure of protein and may render it inactive. An example of such change is seen in the case of Sickle cell disease.


Globular proteins have highly unstable structures making them more sensitive to slight changes in pH or temperature. It is due to lack of very strong interactions among the amino acid side chains. Because of their unstable nature, globular proteins need highly optimum conditions to function properly.

It is evident from the example of enzymes that function only under optimum conditions of pH and temperature. Even a slight change in pH or temperature changes the structure of enzymes and renders them inactive.


Denaturation is the process by which proteins lose their secondary and tertiary structure while the peptide bonds remain intact. The protein becomes disorganized and undergoes unfolding. However, the primary structure of a protein is preserved in this process. Denaturation can be carried out by various denaturing agents like heat, pH, acids, bases, detergents, heavy metals, etc.

Under some conditions, the process of denaturation may be reversed, and the protein may fold back into its original tertiary globular structure. However, in most cases, denatured proteins cannot attain their native structure again, even after the removal of denaturing agent. They become permanently disordered. Such denatured proteins are insoluble in water and precipitate out.


Globular proteins are the functional proteins. Almost all the functions of a cell are carried out with the help of globular proteins. They are essential for all the chemical reactions taking place inside or outside the cells within an organism.

The various functions of globular proteins are elaborated with the help of examples below.


Enzymes are globular proteins that catalyze chemical reactions taking place within the living systems. They are essential molecules for life.

Enzymes are needed for reactions that release energy, such as glycolysis, as well as reactions that result in the formation of a new molecule such as synthesis of proteins, DNA, RNA, etc.

Enzymes are also needed for the digestion of food consumed by living organisms.

Enzymes need highly optimum temperature and pH for their proper functioning. Even a slight change in pH or temperature renders them inactive, making them unable to perform their role.

As enzymes, globular proteins are needed for the basic metabolic process that represent life. Without these proteins, life cannot exist.

Cell Surface Receptors

Globular proteins are also found in all cell membranes. Some of these membrane proteins act as cell surface receptors. The signaling molecules like hormones, neurotransmitters, etc. perform their action by binding to these receptor molecules.

The signalling molecules bind the extracellular face of such proteins. Once a molecule is bound to the receptor protein, the cellular face starts a cascade of reactions within the cytoplasm. In this way, the message carried by the signaling molecule is translated within the cell.


Immunoglobulins are also called antibodies. These are the globular proteins found in the blood. They are an important component of our immune system. Antibodies recognize the antigens and bind them, initiating an immune response. The immune response thus generated protects our body against the foreign harmful invading agents.

Thus, as immune globulins, globular proteins play their role in protecting our bodies from harmful agents.

Transport Proteins

Various globular proteins act as transport proteins carrying different substances in the body. Some examples of these transport proteins include haemoglobin, myoglobin, albumin, haptoglobin, ceruloplasmin, etc. A brief detail of these transport proteins is mentioned below.


It is a globular protein found in red blood cells. Haemoglobin is the primary oxygen transporter in our body. It is made up of four polypeptide chains. It carries oxygen from the lungs to the peripheral areas of the body.

When the blood goes to the lungs, oxygen from air in the alveoli diffuses into the blood and gets attached to haemoglobin. One haemoglobin molecule can bind four molecules of oxygen. As the blood passed through the capillaries of peripheral body parts, oxygen molecules are released by haemoglobin. Thus, oxygen diffuses out of the blood into the extracellular fluid surrounding cells.

Read more about Haemoglobin


Myoglobin is another globular protein involved in the process of oxygen transport. It consists of a single polypeptide chain. Myoglobin carries oxygen from tissues spaces to the cell cytoplasm. It has higher affinity for oxygen as compared to haemoglobin. The increased affinity of myoglobin allows it to bind to oxygen released by haemoglobin and low concentrations and deliver it to the cell. It also keeps oxygen stored in tissues spaces.


It is a transport protein found in blood plasma. It carries lipid-soluble substances such as fatty acids, steroid hormones, bilirubin, drugs, and calcium to some extent. Albumin is the most abundant plasma protein and thus also contributes to the oncotic effect preventing oedema.


It is a plasma protein that binds to free haemoglobin. The free haemoglobin is released into plasma by the lysis of red blood cells. It captures the extra haemoglobin so that it can be recycled.


It is a copper transporter protein found in plasma. It carries copper molecules and also helps to sequester them.

In addition to these proteins, other transporter proteins are also found in blood such as transferrin, prealbumin, thyroxin binding protein, etc.

Transport Channels

Some globular proteins found in cell membranes act as transport channels for ions and other molecules. They form a conduit for the molecules that cannot simply diffuse through the lipid bilayer membrane. These proteins are thus involved in the process of facilitated diffusion as well as active transport. Some examples of such protein channels are mentioned below.

  • Aquaporins allow the facilitated diffusion of water molecules across the membranes
  • Sodium channels provide a route for sodium ions to be moved into the cell.
  • Potassium channels allow the diffusion of potassium ion out of the cell into the extracellular fluid
  • Different types of glucose transporters (GLUTs) cause the movement of glucose molecules into the cell
  • Sodium-Potassium pump is responsible for active transport of ions against the concentration gradient with the consumption ATP
  • Calcium ions can move into the cell via specialized calcium channels

Haemoglobin – A Classic Example

Haemoglobin is a classic example to understand the structure and properties of globular proteins. One molecule of haemoglobin consists of four polypeptide chains and carried four molecules of oxygen. Different structural details and properties are mentioned below.


The structure of haemoglobin can be studied under four headings.

Primary Structure

Haemoglobin consists of four polypeptide chains; two alpha chains and two beta chains. There are 141 amino acids in each alpha chain and 146 amino acids in each beta chain, making a total of 574 amino acids.

Each chain of haemoglobin consists of a heme part and a globin part. Heme consists of a protoporphyrin ring and an iron atom at its centre. The iron atom is kept in place by binding to four nitrogen atoms of the protoporphyrin ring.

Secondary Structure

The amino acids in each polypeptide chain of haemoglobin (alpha and beta) are arranged to form eight alpha-helices. The alpha helices are terminated either by the presence of proline residues or by beta bends and loops.

The alpha-helices in each chain are labeled from A to H. The heme portion rests in the center of each chain. The iron atom present in heme forms a bond with alpha helices and keeps it in place.

Tertiary Structure

Tertiary structure of haemoglobin is formed by the folding of amino acids in alpha and beta chains. Each chain acts as a separate domain. The folding of amino acids in one chain is not affected by folding in the other chain.

The folding of the polypeptide chain takes place in such a way that non-polar amino acids are present in the core of each chain while the polar amino acids are present on the outer surface. Thus, heme portion present in the center of each chain is surrounded by non-polar amino acids.

Quaternary Structure

A molecule of haemoglobin consists of two dimers. Each dimer is constituted by one alpha chain and one beta chain.

The alpha and beta chains in one dimer are held together via hydrophobic interactions among the non-polar molecules. A few of non-polar molecules are present on surface which allow these interactions.

In contrast to this, the two dimers are held together by polar bonds.

This shows how two or domains interact together to form the final structure of a globular protein.


Like other globular proteins, haemoglobin has a globular shape, is soluble in water, has a highly specific amino acid sequence and undergoes denaturation upon changing temperature and pH.

The amino acid sequence is so specific that the change of only one amino acid can distort its structure and render it ineffective. An example is sickle cell disease.

In sickle cell disease, polar glutamic acid at position 6 of the beta chain is replaced by non-polar valine. As a result, haemoglobin precipitates and causes the sickling of red blood cells. It causes severe anemia in patients.

The example of sickle cell anaemia/disease helps to understand the importance of the specific amino acid sequence of globular proteins.


  • Globular proteins are the functional proteins needed for various functions in living organisms.
  • They consist of domains that undergo independent folding as guided by the primary sequence of amino acids.
  • Each domain undergoes independent folding that is facilitated by specialized proteins called chaperons.
  • Domains are stabilized by different kinds of bonds, and later interact together to form the final protein molecule.
  • Globular proteins are spherical in shape and are soluble in water.
  • They have highly irregular but specific amino acid sequence.
  • Globular proteins are highly unstable and undergo denaturation upon slight changes in the environment.
  • Enzymes are globular proteins needed for all the metabolic processes in living systems.
  • As cell surface receptors, globular proteins play their role in coordination and control of body.
  • Haemoglobin, myoglobin, albumin, ceruloplasmin, etc. are some transport proteins that are globular in nature.
  • They also act as transport channels for facilitated diffusion or active transport of molecules into or out of the cell.
  • As immunoglobulin, they are involved in providing protection to the body by detecting the foreign antigen and binding to it, generating an immune response.
  • Haemoglobin is a classic example to study the structure and properties of globular proteins.
  • The primary structure of haemoglobin consists of specific arrangement of 574 amino acids in two alpha chains and two beta chains.
  • The secondary structure consists of formation of alpha helices separated by proline molecules or beta loops, etc.
  • In tertiary structure, each alpha and beta chain undergo independent folding, so that heme group lies in the center of each, surrounded by non-polar amino acids.
  • The quaternary structure envisions haemoglobin as a molecule consisting of two dimers, each formed by one alpha chain and one beta chain.
  • Sickle cell disease can be studied to understand the importance of specific amino acid sequence in globular proteins.

Frequently Asked Questions

What does it mean when a protein is globular?

Based on the gross structure of the molecule, proteins are divided into two types; fibrous proteins and globular proteins. Globular proteins are those in which various amino acids are folded to form a 3D shape that may resemble a ball, a globe, a cigar, etc.

What are 3 examples of globular proteins?

Examples of globular proteins include albumin (a transport protein present in the blood), haemoglobin (an oxygen-carrying protein present in red blood cells), and antibodies (that participate in immune response).

What are globular proteins used for?

Globular proteins perform a variety of functions. Enzymes are globular proteins that act as catalysts in biological reactions, albumin, haemoglobin etc. transport proteins, antibodies are involved in immune response, ferritin is a storage protein that is globular in nature and many more. 

Which protein is Insulin?

Insulin is known as a small globular protein that is made up of only two peptide chains, A and B. A chain contains 21 amino acids while B chain contains 3 amino acids.


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