The structure, molecular interactions and bioactivities of proinsulin C-peptide correlate with a tripartite molecule.
Many biological roles have been assigned to proinsulin C-peptide over the years. Some appear surprisingly disparate and sometimes even contradictory, like chaperone-like actions and depository tendencies. This review summarizes recently reported biomolecular interactions of the peptide and presents how they correlate with structural and functional aspects into a partitioned molecular architecture. At the structural level, the C-peptide sequence and fold can be subdivided into three distinct parts ('tripartite'). At the functional level, its chaperone-like abilities, self-assembly, and membrane interactions, as well as interactions with relevant proteins can be separately ascribed to these three segments. At the biological level, the assignments are compatible with the suggested roles of C-peptide in granular insulin storage, chaperone-like activities on insulin oligomers, possible depository tendencies, and proposed receptor interactions. Finally, the assignments give interesting parallels to further bioactive peptides, including glucagon and neurotensin. Provided pharmaceutical and clinical trials are successfully completed, the present interpretations should supply mechanistic explanations on C-peptide as a bioactive compound of importance in health and diabetes.
Michael
M
Landreh
Jan
J
Johansson
John
J
Wahren
Hans
H
Jörnvall
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002096:C-Peptide / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence; D003920:Diabetes Mellitus / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
D002096:C-Peptide; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D011384:Proinsulin