The hormone insulin is a protein consisting of 2 polypeptide chains.
In the beta cells within islets of Langerhans of the pancreas, insulin is originally produced as a single molecule (preproinsulin) composed of 110 amino acids. After this has passed through the endoplasmic reticulum, 24 amino acids ("the signal peptide") are removed by enzyme action from one end of the chain, leaving another form (pro-insulin), which folds and bonds to give the molecule much of the final structure. This passes into vesicles budded off from the Golgi body. Here a middle section ("the C chain") of 33 amino-acids is removed by the action of the enzymes prohormone convertase 1 and 2, converting it into the final structure with 2 chains, A and B, and 2 amino acids are then removed by another enzyme carboxypeptidase E.
A chain (21 amino acid residues):
Aa no |
1 |
2 |
N-terminal |
GLY |
ILE |
3 |
4 |
5 |
6 |
7 |
8 |
VAL |
GLU |
GLN |
CYS |
CYS |
THR |
9 |
10 |
11 |
12 |
13 |
14 |
SER |
ILE |
CYS |
SER |
LEU |
TYR |
15 |
16 |
17 |
18 |
19 |
20 |
21 |
|
GLN |
LEU |
GLU |
ASN |
TYR |
CYS |
ASN |
C-terminal |
B chain (30 amino acid residues):
Aa no |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
N terminal |
PHE |
VAL |
ASN |
GLN |
HIS |
LEU |
CYS |
GLY |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
16 |
ASP |
HIS |
LEU |
VAL |
GLU |
ALA |
LEU |
TYR |
17 |
18 |
19 |
20 |
21 |
22 |
23 |
24 |
LEU |
VAL |
CYS |
GLY |
GLU |
ARG |
GLY |
PHE |
25 |
26 |
27 |
28 |
29 |
30 |
|
PHE |
TYR |
THR |
PRO |
LYS |
THR |
C terminal |
These sequences are written using standard 3-letter codes for the 20 amino acids. There is a peptide bond between each amino acid, so they are called residues because -H is removed from each intervening amino group, and -OH from the next -COOH group. At one end of each chain (the N terminal end) is an amino group, and at the other end (the C terminal end) is a carboxylic acid group.
Insulin produced in other organisms may have a slightly different amino acid sequence, or extra amino acids, but the next levels of structure are not greatly altered by these variations.
Some of the joined amino acid residues coil to form short sections of alpha helix, due to hydrogen bonds between >N-H and >C=O groups (projecting from peptide bonds of amino acids 3 or 4 residues further along), which stabilises the structure. Other amino acids give a turn to the amino acid chains so the overall structure is fairly compact.
The A chain, which is fairly compact, contains 2 sections of alpha helix (A2 Ile - A8 Thr and A13 Leu - A19 Tyr). In between these sections is a fairly flat ribbon which enables these helices to lie alongside one another, and also brings the side chains of A2 Ile and A19 Tyr into Van der Waals contact.
The B chain appears to wrap around the A chain. It consists of a larger section of alpha-helix (B9 Ser - B19Cys) and the smaller glycine residues at 20 and 23 allow it to fold into V shape. This brings the C terminal residues B24 Phe and B26 Tyr into Van der Waals contact with B15 Leu and B11 Leu of the alpha-helix.
Key figures
Langerhans (identified different looking "islands" amongst the glandular tissue of the pancreas)
Banting and Best (performed physiological experiments on the basis of diabetes)
Dorothy Hodgkin née Crowfoot used X-ray crystallography to reveal the 3-D structure of the insulin molecule (and other important Biological molecules - Nobel prize winner 1964 for work with vitamin B12) - see link below
Sanger (worked out the primary structure of insulin, 1958 Nobel Prize winner).