The activity of prolactin releasing peptide correlates with its helicity.

Deluca SH, Rathmann D, Beck-Sickinger AG, Meiler J
Biopolymers. 2013 99 (5): 314-25

PMID: 23426574 · PMCID: PMC3580954 · DOI:10.1002/bip.22162

The prolactin releasing peptide (PrRP) is involved in regulating food intake and body weight homeostasis, but molecular details on the activation of the PrRP receptor remain unclear. C-terminal segments of PrRP with 20 (PrRP20) and 13 (PrRP8-20) amino acids, respectively, have been suggested to be fully active. The data presented herein indicate this is true for the wildtype receptor only; a 5-10-fold loss of activity was found for PrRP8-20 compared to PrRP20 at two extracellular loop mutants of the receptor. To gain insight into the secondary structure of PrRP, we used CD spectroscopy performed in TFE and SDS. Additionally, previously reported NMR data, combined with ROSETTANMR, were employed to determine the structure of amidated PrRP20. The structural ensemble agrees with the spectroscopic data for the full-length peptide, which exists in an equilibrium between α- and 3(10)-helix. We demonstrate that PrRP8-20's reduced propensity to form an α-helix correlates with its reduced biological activity on mutant receptors. Further, distinct amino acid replacements in PrRP significantly decrease affinity and activity but have no influence on the secondary structure of the peptide. We conclude that formation of a primarily α-helical C-terminal region of PrRP is critical for receptor activation.

Copyright © 2012 Wiley Periodicals, Inc.

MeSH Terms (24)

Amino Acid Sequence Animals Binding Sites Cell Line, Tumor Chlorocebus aethiops Circular Dichroism COS Cells Humans Hydrogen-Ion Concentration Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Mutation Prolactin-Releasing Hormone Protein Binding Protein Conformation Protein Stability Protein Structure, Secondary Receptors, Neuropeptide Signal Transduction Sodium Dodecyl Sulfate Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Temperature Trifluoroacetic Acid

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