ISSN:
0006-3525
Keywords:
parathyroid hormone
;
parathyroid hormone-related protein
;
G-protein coupled receptors
;
peptide conformations in micelles
;
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The third-cytoplasmic loop of the G-protein coupled receptor responsible for the activity of parathyroid hormone and parathyroid hormone-related protein has been structurally characterized in aqueous solution in the presence of sodium dodecylsulfate and dodecylphosphocholine micelles. The high-resolution conformation of the 29-amino acid peptide containing the sequence of the cytoplasmic loop was obtained by CD and nmr. The structure was refined using a two-step distance geometry based method that first includes the removal of all side chains to quickly locate the globular fold of the peptide. After a simulated annealing protocol, the side chains are added in a random fashion. The resulting conformation was further refined with nuclear Overhauser enhancement restrained molecular dynamics using a two-phase simulation cell consisting of carbon tetrachloride and water as a mimetic of the biphasic, hydrophobic/hydrophilic character of the micelles in which the experimental measurements were carried out. The topological orientation of the cycloplasmic loop within the micelle was determined by addition of 5-doxylstearate and monitoring the decrease of nmr signal intensities from the radical-induced relaxation. The conformation and relative orientation of the peptide provided insight into the mechanism by which the cytoplasmic portion of the receptor activates the heterotrimeric, guanine nucleotide-binding regulatory protein, one of the first steps in signal transduction. © 1997 John Wiley & Sons, Inc. Biopoly 40: 653-666, 1996
Additional Material:
12 Ill.
Type of Medium:
Electronic Resource
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