title: N-terminal segment of proinsulin C-peptide active in insulin interaction/desaggregation.
abstract: Evidence has emerged that proinsulin C-peptide has at least three types of functional interactions in addition to its role during synthesis and secretion of insulin. Thus, C-peptide has been shown (i) to bind to cell membranes triggering G-protein-mediated intracellular signaling; (ii) to be internalized into cells and nuclei promoting transcription of rRNA and expression of particular genes; and (iii) to interact with peptides, including insulin, causing desaggregation of insulin oligomers like a chaperone, and with itself, causing homo-oligomers potentially capable of forming aggregates and deposits. In this work, we studied the insulin-C-peptide interactions by monitoring desaggregation and binding effects of C-peptide fragments on insulin. We find that the N-terminal segment of C-peptide harbors an interaction with insulin and that Glu11 appears to play a role in this action. We conclude that C-peptide fragments with this residue can mimic C-peptide in biophysical interactions with insulin, and that the insulin-interacting and membrane-interacting effects of C-peptide are distinct, ascribable to separate C-peptide segments, N- and C-terminally, respectively. The findings may have relevance to peptide effects in diabetic and healthy states.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nerelius
authors.forename: Gunvor
authors.initials: G
authors.lastname: Alvelius
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000595:Amino Acid Sequence; D002096:C-Peptide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008969:Molecular Sequence Data
chemical_list: D002096:C-Peptide; D007328:Insulin; D018698:Glutamic Acid