Mammals inhale oxygen from air through their lungs. The oxygen needs a way to be carried from the lungs to the rest of the body for various biological processes. This happens via the blood, specifically the protein hemoglobin, found in red blood cells. Hemoglobin performs this function due to its four levels of protein structure: the primary structure of hemoglobin, the secondary structure, and the tertiary and quaternary structures.

Hemoglobin is a large protein molecule found in red blood cells. In fact, hemoglobin is the substance that lends blood its red hue. Molecular biologist Max Perutz discovered hemoglobin in 1959. Perutz used X-ray crystallography to determine the special structure of hemoglobin. He would also eventually discover the crystal structure of its deoxygenated form, as well as the structures of other important proteins.

Hemoglobin is the carrier molecule of oxygen to the trillions of cells in the body, required for people and other mammals to live. It transports both oxygen and carbon dioxide.

This function occurs because of hemoglobin’s unique shape, which is globular and made of four subunits of proteins surrounding an iron group. Hemoglobin undergoes changes to its shape to help make it more efficient in its function of carrying oxygen. To describe the structure of a hemoglobin molecule, one must understand the manner in which proteins are arranged.

A protein is a large molecule made from a chain of smaller molecules called amino acids. All proteins possess a definitive structure due to their composition. Twenty amino acids exist, and when they bond together, they make unique proteins depending on their sequence in the chain.

Amino acids are comprised of an amino group, a carbon, a carboxylic acid group and an attached sidechain or R-group that makes it unique. This R-group helps determine whether an amino acid will be hydrophobic, hydrophilic, positively charged, negatively charged or a cysteine with disulfide bonds.

When amino acids join together, they form a peptide bond and make a polypeptide structure. This happens via a condensation reaction, resulting in a water molecule. Once amino acids make a polypeptide structure in a specific order, this sequence makes up a primary protein structure.

However, polypeptides do not remain in a straight line, but rather they bend and fold to form a three-dimensional shape that can either look like a spiral (an alpha helix) or a sort of accordion shape (a beta-pleated sheet). These polypeptide structures make up a secondary protein structure. These are held together via hydrogen bonds.

Tertiary protein structure describes a final form of a functional protein comprised of its secondary structure components. The tertiary structure will have specific orders to its amino acids, alpha helices and beta-pleated sheets, all of which will be folded into the stable tertiary structure. Tertiary structures often form in relation to their environment, with hydrophobic portions on the interior of a protein and hydrophilic ones on the exterior (as in cytoplasm), for example.

While all proteins possess these three structures, some consist of multiple amino acid chains. This type of protein structure is called quaternary structure, making a protein of multiple chains with various molecular interactions. This yields a protein complex.

Once one can describe the structure of a hemoglobin molecule, it is easier to grasp how hemoglobin’s structure and function are related. Hemoglobin is structurally similar to myoglobin, used to store oxygen in muscles. However, hemoglobin’s quaternary structure sets it apart.

The quaternary structure of a hemoglobin molecule includes four tertiary structure protein chains, which are all alpha helices.

Individually, each alpha helix is a secondary polypeptide structure made of amino acid chains. The amino acids are in turn the primary structure of hemoglobin.

The four secondary structure chains contain an iron atom housed in what is called a heme group, a ring-shaped molecular structure. When mammals breathe in oxygen, it binds to the iron in the heme group. There are four heme sites for oxygen to bind to in hemoglobin. The molecule is held together by its housing of a red blood cell. Without this safety net, hemoglobin would easily come apart.

Oxygen’s binding to a heme initiates structural changes in the protein, which causes the neighboring polypeptide subunits to change as well. The first oxygen is the most challenging to bond, but the three additional oxygens are then able to bond quickly.

The structural shape changes due to oxygen binding to the iron atom in the heme group. This shifts the amino acid histidine, which in turn alters the alpha helix. The changes continue through the other hemoglobin subunits.

Oxygen is breathed in and binds to hemoglobin in the blood via the lungs. Hemoglobin carries that oxygen in the bloodstream, delivering oxygen to wherever it is needed. As carbon dioxide increases in the body and the oxygen level decreases, oxygen is released and hemoglobin’s shape changes again. Eventually all four oxygen molecules are released.

Hemoglobin not only carries oxygen through the bloodstream, it also binds with other molecules. Nitric oxide can bind to the cysteine in hemoglobin as well as to heme groups. That nitric oxide releases blood vessel walls and lowers blood pressure.

Unfortunately, carbon monoxide can also bond to hemoglobin in a perniciously stable configuration, blocking out oxygen and leading to suffocation of cells. Carbon monoxide does this quickly, making exposure to it very dangerous, as it is a toxic, invisible and odorless gas.

Hemoglobins are not only found in mammals. There is even a type of hemoglobin in legumes, called leghemoglobin. Scientists think this helps bacteria fix nitrogen at the roots of legumes. It bears passing similarity to human hemoglobin, chiefly because of its iron-binding histidine amino acid.

As mentioned above, hemoglobin’s structure changes in the presence of oxygen. In a healthy person, it is normal to have some individual differences in hemoglobin’s primary structure of amino acid configurations. Genetic variations in populations reveal themselves when there are problems with hemoglobin structure.

In sickle-cell anemia, a mutation in the amino acid sequence leads to a clumping of deoxygenated hemoglobins. This alters the shape of red blood cells until they resemble a sickle or crescent shape.

This genetic variation can prove to be deleterious. Sickle cell red blood cells are vulnerable to damage and hemoglobin loss. This in turn results in anemia, or low iron. Individuals with sickle cell hemoglobins do possess an advantage in areas prone to malaria.

In thalassemia, the alpha helices are not produced in the same way, negatively affecting hemoglobin.

Because of challenges in storing blood and matching blood types, researchers seek a way in which to make artificial blood. Work continues on making new hemoglobin types, such as one with two glycine residues that keep it bound together in solution, rather than coming apart in the absence of a protective red blood cell.

Knowing the four levels of protein structure in hemoglobin helps scientists come up with ways to better understand its function. In turn, this could lead to novel targeting of pharmaceuticals and other medical treatments in the future.