title: C-peptide evolution: generation from few structural restrictions of bioactivities not necessarily functional.
abstract: The proinsulin C-peptide has molecular, cellular and organismal activities but lacks disease-associated mutations or short-term loss-of-function effects. This dilemma between activity and function may be explained from its evolutionary setting with insulin as an ancestral partner. The charge, approximate length and flexibility of C-peptide are all that is required for the insulin interactions, while remaining aspects are free to evolve, where new bioactivities can emerge. They can initially be transient, weak, and non-functional, but may gradually be consolidated. In this manner, C-peptide may have acquired multiple bioactivities, explaining why some yet have limited functions but could represent early-stage hormonal-like activities.
authors.affiliation: Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Landreh
authors.affiliation: Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: Hans.Jornvall@ki.se.
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002096:C-Peptide / Q000737:chemistry / Q000502:physiology*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D002096:C-Peptide
keywords: Bioactive peptide; Hormonogenesis; Molecular evolution; Proinsulin C-peptide; Structural variability