Insulin is composed of two peptide chains referred to as the A chain and B chain. A and B chains are linked together by two disulfide bonds, and an additional disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids.
Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Molecular Structure of insulin: The insulin monomer and its assembly. U Derewenda , U Derewenda.
Department of Chemistry,University of York. Oxford Academic. Google Scholar. Z Derewenda. G G Dodson. Insulin is a peptide hormone composed of 51 amino acids and has a molecular weight of Da. It is produced in the islets of Langerhans in the pancreas. The name comes from the Latin insula for "island". Insulin's structure varies slightly between species of animals. Insulin from animal sources differs somewhat in "potency" in humans because of those variations.
Pig insulin is especially close to the human version. Insulin was the first protein whose amino acid sequence was identified and the first to be synthesized. It is initially synthesized as a precursor molecule known as proinsulin and on cleavage it gives two peptides chains, one comprising of 21 amino acids and the other of 30 amino acids, being mostly conserved in humans and animals [6] see Figure 1.
The two chains are joined together by two disulfide bonds between two cysteine residues, where a disulfide bond is the linkage bond between two sulfurs as shown below.
Figure 1. The two chains comprising the insulin structure, A and B, indicating also a disulfide bond between cysteines R represents the molecular fragment coloured in blue , since they are very important in stabilizing the two chains together.
Chain structure from Ref. Espinal says in his book [6] that X-ray analysis in showed that insulin exists as hexameric rhombohedral crystals and that its dimeric form has a relative molecular weight of Each hexamer is either bound to two zinc ions or to four zinc ions. There is also a calcium binding site, and finally any other available sites are occupied by water molecules or another ligand [7]. The hexamer and some of its binding sites are indicated by Figure 2.
The insulin hexamer with two of the main binding sites shown next to it. From Ref. In addition, it is very important to realize that most of hormone functions are more potent once the 3D structure is obtained.
Consequently modifications on any of the amino-acids of the two chains or any conformational changes alter the activity as well [9]. Finally, it is worth mentioning that achievements to build up newly modified structures have been done, as reported by Schuttler and Brandenburg [10], by cross-linking, for example, insulin dimers together, since such alterations can be very helpful in obtaining more information on insulin-secretion mechanisms and action.
Starting from the very early times, in around , Minkowski and Von Mering, used pancreas from dogs to produce and study the different effects that diabetics exhibited, since the pancreas is the major tissue where insulin is involved. Toggle navigation PDB Educational portal of. Molecule of the Month. Insulin The hormone insulin helps control the level of glucose in the blood Insulin and proinsulin, with A-chain in green, B-chain in blue and disulfide linkages in yellow.
Our cells communicate using a molecular postal system: the blood is the postal service and hormones are the letters. Insulin is one of the most important hormones, carrying messages that describe the amount of sugar that is available from moment to moment in the blood. Insulin is made in the pancreas and added to the blood after meals when sugar levels are high.
This signal then spreads throughout the body, binding to insulin receptors on the surface of liver, muscle and fat cells. Insulin tells these organs to take glucose out of the blood and store it, in the form of glycogen or fat. Insulin is a tiny protein. It moves quickly through the blood and is easily captured by receptors on cell surfaces, delivering its message. Small proteins pose a challenge to cells: it is difficult to make a small protein that will fold into a stable structure.
Our cells solve this problem by synthesizing a longer protein chain, which folds into the proper structure. Then, the extra piece is clipped away, leaving two small chains in the mature form. These two chains are shown in the lower diagram in blue and green, for insulin from pigs PDB entry 4ins. The structure is further stabilized by three disulfide bridges, one of which is seen in yellow in each illustration.
When insulin function is impaired, either by damage to the pancreas or by the rigors of aging, glucose levels in the blood rise dangerously, leading to diabetes mellitus.
For people totally deficient in insulin, such as children that develop diabetes early in life, this can be acutely dangerous.
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