Part:BBa_K3003023
Wild-Type Insulin with a Linker Peptide
The wild type insulin consists of A and B chains. These chains are connected via a C-peptide (connecting peptide) when insulin is first translated. C-peptide is responsible for orienting A and B chains to enable folding. After translation, a hydrophobic N-terminal signal sequence is attached to this protein sequence. This form of insulin is called preproinsulin. The N-terminal signal sequence facilitates the translocation of preproinsulin across the rough ER membrane. During translocation to ER, the signal peptide is cleaved from preproinsulin by a signal peptidase. This cleavage yields proinsulin. Proinsulin undergoes folding and formation of disulfide bonds. After gaining a 3-D confirmation in ER, proinsulin is transported to Golgi. This is where the C-peptide between A and B chains are cleaved. The cleavage of C-peptide is not possible in bacteria. However, insulin with an uncleaved C-peptide is not proper for receptor binding. Thus, insulin chains are connected via a linker peptide in this part. The linker peptide will not be cleaved, resulting in a single chain insulin (SCI) consisting insulin A chain, linker and insulin B chain. It was shown in previous studies that SCIs can bind to the insulin receptor. The linker peptide chosen for this part is taken from a 1996 patent design having the patent code EP0741188A2 of European Patent Office.
Sequence and Features
- 10INCOMPATIBLE WITH RFC[10]Illegal PstI site found at 115
- 12INCOMPATIBLE WITH RFC[12]Illegal PstI site found at 115
- 21INCOMPATIBLE WITH RFC[21]Illegal XhoI site found at 103
- 23INCOMPATIBLE WITH RFC[23]Illegal PstI site found at 115
- 25INCOMPATIBLE WITH RFC[25]Illegal PstI site found at 115
- 1000COMPATIBLE WITH RFC[1000]
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