3D Structure of Insulin

CPK Color Scheme

Discovered in 1921 by Sir Frederick Grant Banting and Charles Herbert Best, insulin is a protein in the human body that plays a key role in the metabolism of carbohydrates as it is involved in one part of the process, which converts food into fuel (Kane and Rivers).

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To display the molecule as four distinct peptide chains click here. Insulin is manufactured in considerable amounts by the beta cells of the pancreatic islets of Langerhans, a small section of the pancreas (Kane and Rivers). It is very difficult for small proteins to fold into stable structures, so to avoid this problem larger precursors of insulin are synthesized first (Goodsell, 2001). So the form of insulin that you are viewing here has four chains, whereas the active form of insulin is made up of only two chains, A and B. The A chain and the C chain are both comprised of 21 residues, while the B and D chains both contain 30 residues. The A chain is represented in dark blue, the B chain in light blue, the C chain in green and the D chain in yellow. Note that the red chains are not apart of the insulin structure, but have just been complexed with it to provide structural stability. To learn more about how insulin is processed into its active form click the link below.

Insulin Synthesis

The four chains are held together by disulide bonds . These bonds are made up of two cysteine amino acids that lie across from each other within the protein. Insulin has three disulfide bonds, two of which attach the A and B chains to each other, which are represented by the faint dotted lines between the dark and light blue chains. These three disulfide bridges occur between: 1) The 6th amino acid on the A chain and the 11th amino acid on the A chain. 2) The 7th amino acid on the A chain and the 7th amino acid on the B chain. 3) The 20th amino acid on the A chain and the 19th amino acid on the B chain (Qiao, 2003).

To see the active form of insulin click here. The active form of insulin only consists of the A and B chains, which are seen here in dark and light blue, respectively.

To view the the secondary folding structures of the insulin chains click here. The A (dark blue) chain has three alpha helices, the B chain (light blue) has two alpha helices, the C chain (green) has three alpha helices, and the D chain (yellow) has two alpha helices.

Further secondary structures are the beta sheets, which are found only in the B and D chains. Both of these chains contain one beta sheet shown here in orange.

The structure of insulin is very stable because there is a collection of carbon-rich amino acids (i.e.: leucine and isoleucine) in the center of the protein, which are shown here as white ribbons, so and insulin has a hydrophobic (water-fearing) center (Goodsell, 2001), which is then surrounded on the outside by hydrophilic (water-loving), charged amino acids (i.e.: arginine, glutamine and lysine), seen here in violet (Goodsell, 2001) .

The amino acid sequence for insulin is highly conserved among vertebrates to the point where we have been able to use bovine and porcine insulin for people who cannot produce their own insulin (Bowen, 2000). In fact, insulin from pigs differs by only one amino acid: threonine in humans and alanine in pigs. Click here to view the insulin hexamer with the threonines highlighted in magenta. There are only two threonines on the B chain (light blue), and the one that is farther to left and higher up on this chain is the threonine, which gets switch to alanine in pigs.