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Solution structure of human proinsulin C‐peptide
Author(s) -
Munte Claudia Elisabeth,
Vilela Luciano,
Kalbitzer Hans Robert,
Garratt Richard Charles
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04843.x
Subject(s) - proinsulin , pentapeptide repeat , peptide , chemistry , stereochemistry , molecule , nuclear magnetic resonance spectroscopy , turn (biochemistry) , biochemistry , biology , insulin , organic chemistry , endocrinology
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% H 2 O/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.