3D Structure of INSULIN

Insulin is a protein in the human body that plays a major role in decreasing the levels of glucose in the blood and regulating the metabolism of glucose, fats, and proteins (Lilly, 1996). There are different versions of the insulin protein, but this chime image specifically focuses on human insulin.

The active version of the insulin hormone is not created immediately upon food entering the body. There are steps this protein takes in order to make the version to be used successfully in the human body. Once food enters the body, it immediately is detected and the insulin mRNA is translated as a single chain precursor called preproinsulin in the pancreas. The preproinsulin, made up of an A, B, and C chains, and a signal peptide, is 110 amino acids long. Soon after, the preproinsulin has its signal peptide removed as it enters the endoplasmic reticulum and proinsulin is made. Proinsulin is 86 amino acids long, containing the A, B, and C chains. In order to make active insulin for the body to use properly, proinsulin is then exposed to several specific endopeptidases to excise the C chain. All is left is the A and B chains, which is considered the insulin hormone.
Find out more information about Insulin.

To reset molecule to its original wire image, click here.
Highlight the individual A and B chains of this insulin molecule. Click here.

To see the A and B chains in a ribbon image, click

Insulin is made of an A chain that has 21 amino acids. Click here to highlight the A chain in yellow.

Chain A is made up of 2 alpha helices. The first alpha helix (shown in green) is from isoleucine (A2) to threonine (A8). The second alpha helix (shown in pink) is a little larger and is from serine (A12) to asparagine (A18).

Chain A also has 3 disulphide bonds. One connects chain A in two places (A6 to A11), and 2 of the bonds are connected to chain B. Click here to see the disulphide bond connected two places on the A chain (dotted lines in green).

Insulin is also made of a B chain that has 30 amino acids. Click here to highlight the B chain in light green.

Chain B is made up of only 1 alpha helix. This helix is from serine (B9) to cysteine (B19) (highlighted in violet).

Chain B also has 2 disulphide bonds that bond to Chain A (A7 to B7 and A20 to B19). Chain B is red, chain A is blue. The 2 disulphide bonds are seen in blue and red dotted lines.

Chain B also has 2 beta turns. Beta turns are an important step in the protein folding pathway . These two beta turns link the beta-sheets with hydrogen bonds of Chain B to create a beta-hairpin (Drakos, 2001). This is part of the secondary structure of this protein. The area where the beta turn exists is highlighted in yellow, from B20-B23 and B24-B28.

Click here to see the N terminus of the molecule. (B1-B8)
Click here to see the C terminus of the molecule. (A1-A2)

The insulin protein has a hydrophobic center due to its carbon rich amino acids which line the inner part of the A and B chains. Click here to see the hydrophobic amino acids (seen in pink). The amino acids that create this hydrophobic center are maily leucine, isoleucine, valine, and glycine. From this image we can see that the middle of the two chains is predominantly hydrophobic (it is pink).

On the outside of insulin, most of the amino acids are charged and create a hydrophilic nature. Click here to seen the hyrdophilic amino acids (shown in green). The amino acids most charged on the protein are arginene, geutamine, and lysine. These charged amino acids make the outside parts of the molecule hydrophilic.

Conservation of Insulin

The most conserved organism that carries insulin, is the pig. the pig has the exact amino acid sequence as human insulin, differing in only one amino acid. In place of threonin (T) in human insulin, the pig has alanine (A). Click here to see where this difference occurs (appears in yellow).

Click here to see insulin conservation within the amino acid sequence. In this image, the degree of conservation is shown by an array of colors. From highest to lowest conservation: red, orange, yellow, light blue, purple, dark blue. This shows that most conservation remains in the hydrophobic center of the insulin molecule, where as the tails are less conserved.

Possible Changes to cause mild form of diabetes

These new forms within the "insulin-like" family have significantly changed the receptor binding affinity.
Upon three mutations in the human insulin gene, abnormal insulin results with a reduced receptor binding affinity (Steiner, et. al, 1985). These single base mutations are associated with a syndrome of mild diabetes because they are located in important regions of the B chain that contribute to the receptor binding region.

The mutations occur in the restriction site MboII, so the protein loses this cleavage site and it eventually can cause damage and lead to carbohydrate intolerance in the body. Click here to see where the mutations occur - point mutations within the three amino acids: Arginine, Glycine, and Phenylalanine.