Acidic residues on the N-terminus of proinsulin C-Peptide are important for the folding of insulin precursor.

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Chen LM, Yang XW, Tang JG

Acidic residues on the N-terminus of proinsulin C-Peptide are important for the folding of insulin precursor.

J Biochem. 2002 Jun;131(6):855-9.

PubMed ID

12038982 [ View in PubMed

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Abstract

To investigate the role of C-peptide in the folding of insulin precursor, a series of C-peptide mutant proinsulin genes were constructed, overexpressed in Escherichia coli and the proteins purified. Correct disulfide linkages of these proteins were confirmed by both tryptic peptide mapping and insulin receptor binding analyses. In vitro refolding experiments were performed with the purified proteins and showed that mutations on the glycine-rich middle segment of C-peptide, GGGPGAG, and deletion of the C-terminal pentapeptide, EGSLQ, as well as mutations on the two pairs of dibasic residues at the two ends of C-peptide did not significantly affect the refolding yields. However, both alanine replacement mutation and deletion of three highly conserved acidic residues (EAED) at the N-terminus of the C-peptide resulted in serious aggregation during refolding. The results indicate that the highly conserved acidic N-terminal part of C-peptide is very important for insulin precursor folding, and that C-peptide may have some intramolecular chaperone-like function in the folding of insulin precursor.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Insulin human	Insulin receptor	Protein	Humans	Yes	Agonist	Details
Insulin pork	Insulin receptor	Protein	Humans	Yes	Binder	Details