Molecular interaction between kisspeptin decapeptide analogs and a lipid membrane

Ju Yeon Lee, Jung Sun Moon, Young Jae Eu, Chul Won Lee, Sung Tae Yang, Seung Kyu Lee, Hyun Ho Jung, Ha Hyung Kim, Hyewhon Rhim, Jae Young Seong, Jae Il Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Kisspeptin-10 is the C-terminal decapeptide amide of kisspeptin, an endogenous ligand for GPR54, and exhibits the same binding and agonist activity as the parent molecule. Although GPR54 is a membrane-embedded protein, details of the molecular interaction between kisspeptin-10 and lipid membranes remain unclear. Here, we performed a series of structural analyses using alanine-scanning analogs of kisspeptin-10 in membrane-mimetic medium. We found that there is a close correlation between lipid membrane binding and agonist activity. For instance, the F10A and non-amidated (NH2 → OH) analogs showed little or no GPR54-agonist activity and elicited no blue shift in tryptophan fluorescence. NMR analysis of kisspeptin-10 analog in DPC micelles revealed it to contain several tight turn structures, encompassing residues Trp3 to Phe10, but no helical conformation like that seen previously with SDS micelles. Together, our results suggest that kisspeptin-10 may activate GPR54 via a ligand transportation pathway incorporating a lipid membrane.

Original languageEnglish
Pages (from-to)109-114
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume485
Issue number2
DOIs
Publication statusPublished - 2009 May 15

Keywords

  • DPC
  • GPR54
  • Kisspeptin
  • NMR
  • Peptide-membrane interaction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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  • Cite this

    Lee, J. Y., Moon, J. S., Eu, Y. J., Lee, C. W., Yang, S. T., Lee, S. K., Jung, H. H., Kim, H. H., Rhim, H., Seong, J. Y., & Kim, J. I. (2009). Molecular interaction between kisspeptin decapeptide analogs and a lipid membrane. Archives of Biochemistry and Biophysics, 485(2), 109-114. https://doi.org/10.1016/j.abb.2009.03.002