Structure of glucagon-like peptide (7-36) amide in a dodecylphosphocholine micelle as determined by 2D NMR.
We have used 2D 1H NMR to determine the structure of glucagon-like peptide-1-(7-36) amide bound to a dodecylphosphocholine micelle. In this membranelike environment, the peptide hormone is shown to have a structure similar to that observed for glucagon. It consists of an N-terminal random coil segment (residues 1-7), two helical segments (7-14 and 18-29), and a linker region (15-17). The C-terminal helix is more stable than the N-helix as determined by amide proton exchange experiments. The C-terminal helix shows much larger alpha and amide proton upfield secondary shifts relative expected for a random coil conformation. This suggests a highly helical structure in this portion of the molecule. The C-terminal helix also has a much larger fraction of residues that are hydrophobic, presumably enhancing the interaction of this portion of the peptide with the micelle (or membrane). The structure refined from the NOESY data is not a uniform alpha-helix throughout residues 6-30. A uniform helix would not be perfectly amphiphilic since the hydrophobic face of the N-terminal portion of the helix is positioned in nearly perfect opposition to the hydrophobic face of the C-terminal portion. However, helical distortion around residues 15-17 allows a phase shift of the two helical segments to position nearly all of the hydrophobic residues (and none of the hydrophilic ones) on a single face of the distorted single helix as would be required to favorably interact with the hydrophobic portion of the micelle or membrane.
Thornton
K
K
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907.
Gorenstein
D G
DG
D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives*; D017433:Protein Structure, Secondary
D000577:Amides; D008823:Micelles; D010446:Peptide Fragments; D010767:Phosphorylcholine; C061970:glucagon-like peptide 1 (7-36); C028810:dodecylphosphocholine; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon