Structural motifs in the maturation process of peptide hormones. The somatostatin precursor. I. A CD conformational study.
Synthetic peptides reproducing both the native domain around the dibasic cleavage site of prosomatostatin, and mutated sequences there of, previously assayed in site-directed mutagenesis experiments, have been studied by CD in different solvent systems, such as water, TFE/H2O, MeCN/H2O and aqueous SDS, in order to ascertain the ability of each solvent to stabilize secondary structural motifs. A combination of deconvolution methods and empirical calculations, that allow subtraction of the contributions due to unordered structures from the spectra, suggests that mainly two distinct families of ordered conformers containing alpha-helix and/or structurally different beta-turns are present in solution, the relative stability of the different conformers depending on the nature of the solvent. The presence of beta-turns is in line with a previous NMR study in DMSO and DMSO/H2O. Comparison of the CD spectra in aqueous SDS of peptides undergoing processing with a sequence not processed in vivo shows that only the latter possesses a stable and detectable alpha-helix population. This observation suggests that the structuration involving beta-turns but no alpha-helix, which was observed by CD both in SDS and organic solvent/H2O mixtures at high water contents, might be of biological significance. The similarity of this structuration to molecular models obtained from NMR data in DMSO and DMSO/H2O is discussed.
Simonetti
Mario
M
Department of Chemical Process Engineering, University of Padova, Italy.
Di
Bello Carlo
BC
D000097:Acetonitriles / Q000737:chemistry; D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006728:Hormones / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry*; D011138:Polytetrafluoroethylene / Q000737:chemistry; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013004:Somatostatin / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000737:chemistry
D000097:Acetonitriles; D006728:Hormones; D010455:Peptides; D011498:Protein Precursors; D014867:Water; D013004:Somatostatin; D011138:Polytetrafluoroethylene