Unordered structured of proinsulin C-peptide in aqueous solution and in the presence of lipid vesicles.
Proinsulin C-peptide ameliorates renal and autonomic nerve function and increases skeletal muscle blood flow, oxygen uptake and glucose transport in patients with insulin-dependent diabetes mellitus. These effects have in part been ascribed to the stimulatory influence of C-peptide on Na+,K+-ATPase and endothelial nitric oxide synthase. To evaluate the capacity of C-peptide to insert into lipid bilayers and form ion channels, C-peptide secondary structure and membrane interactions were studied with circular dichroism spectroscopy and size exclusion chromatography. C-peptide is shown to lack a stable secondary structure, both when part of proinsulin and when free in aqueous solution, although the N-terminal third of the peptide exhibits an alpha-helical conformation in trifluoroethanol. Moreover, C-peptide remains disordered in the aqueous solvent in the presence of lipid vesicles, regardless of vesicle composition. In conclusion, C-peptide is unlikely to elicit physiological effects through stable conformation-dependent interactions with lipid membranes.
Henriksson
M
M
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. mikael.henriksson@mbb.ki.se
Shafqat
J
J
Liepinsh
E
E
Tally
M
M
Wahren
J
J
Jörnvall
H
H
Johansson
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002096:C-Peptide / Q000737:chemistry* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008563:Membrane Lipids / Q000378:metabolism*; D008823:Micelles; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000187:drug effects; D051381:Rats; D012996:Solutions; D014270:Trifluoroethanol / Q000378:metabolism / Q000494:pharmacology
D002096:C-Peptide; D008081:Liposomes; D008563:Membrane Lipids; D008823:Micelles; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D012996:Solutions; D014270:Trifluoroethanol; D002784:Cholesterol