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- Title
Solution structure of human proinsulin C-peptide.
- Authors
Munte, Claudia Elisabeth; Vilela, Luciano; Kalbitzer, Hans Robert; Garratt, Richard Charles
- 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 β-turn, whereas the C-terminal region (residues 27–31) presents the most well-defined structure of the whole molecule including a type III′β-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 β-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.
- Subjects
PROINSULIN; PROTEIN precursors; C-peptide; INSULIN; BIOSYNTHESIS; NUCLEAR magnetic resonance spectroscopy; BIOCHEMISTRY
- Publication
FEBS Journal, 2005, Vol 272, Issue 16, p4284
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2005.04843.x