title: Solution structure of human proinsulin C-peptide.
abstract: The C-peptide of proinsulin is important for the biosynthesis of insulin, but has been considered for a long time to be biologically inert. Recent studies in diabetic patients have stimulated a new debate about its possible regulatory role, suggesting that it is a hormonally active peptide. We describe structural studies of the C-peptide using 2D NMR spectroscopy. In aqueous solution, the NOE patterns and chemical shifts indicate that the ensemble is a nonrandom structure and contains substructures with defined local conformations. These are more clearly visible in 50% H2O/50% 2,2,2-trifluoroethanol. The N-terminal region (residues 2-5) forms a type I beta-turn, whereas the C-terminal region (residues 27-31) presents the most well-defined structure of the whole molecule including a type III'beta-turn. The C-terminal pentapeptide (EGSLQ) has been suggested to be responsible for chiral interactions with an as yet uncharacterized, probably a G-protein-coupled, receptor. The three central regions of the molecule (residues 9-12, 15-18 and 22-25) show tendencies to form beta-bends. We propose that the structure described here for the C-terminal pentapeptide is consistent with the previously postulated CA knuckle, believed to represent the active site of the C-peptide of human proinsulin.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil.
authors.forename: Claudia Elisabeth
authors.initials: CE
authors.lastname: Munte
authors.forename: Luciano
authors.initials: L
authors.lastname: Vilela
authors.forename: Hans Robert
authors.initials: HR
authors.lastname: Kalbitzer
authors.forename: Richard Charles
authors.initials: RC
authors.lastname: Garratt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D011384:Proinsulin / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012996:Solutions
chemical_list: D010455:Peptides; D012996:Solutions; D011384:Proinsulin