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The activity of prolactin releasing peptide correlates with its helicity
Author(s) -
DeLuca Stephanie H.,
Rathmann Daniel,
BeckSickinger Annette G.,
Meiler Jens
Publication year - 2013
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22162
Subject(s) - chemistry , peptide , receptor , protein secondary structure , mutant , amino acid , helix (gastropod) , biochemistry , prolactin , nuclear magnetic resonance spectroscopy , stereochemistry , biology , hormone , ecology , snail , gene
Abstract 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 R OSETTA NMR, 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. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 273–281, 2013.