Stephanie H. DeLuca and Daniel Rathmann contributed equally to this work.
Article first published online: 20 FEB 2013
Copyright © 2012 Wiley Periodicals, Inc.
Volume 99, Issue 5, pages 314–325, May 2013
How to Cite
DeLuca, S. H., Rathmann, D., Beck-Sickinger, A. G. and Meiler, J. (2013), The activity of prolactin releasing peptide correlates with its helicity. Biopolymers, 99: 314–325. doi: 10.1002/bip.22162
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at email@example.com
- Issue published online: 20 FEB 2013
- Article first published online: 20 FEB 2013
- Accepted manuscript online: 25 SEP 2012 06:25AM EST
- Manuscript Accepted: 15 SEP 2012
- Manuscript Revised: 30 AUG 2012
- Manuscript Received: 25 JUN 2012
- DFG. Grant Numbers: SFB 610, BE 1264-11
- NIH. Grant Numbers: R01 MH090192, R01 GM GM080403
- PrRP receptor;
- RF-amide peptide;
- chemical shifts;
- protein folding;
- peptide receptor;
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 310-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.