Molecular interaction between kisspeptin decapeptide analogs and a lipid membrane
| Autor: | Jae Il Kim, Jung Sun Moon, Sung-Tae Yang, Hyewhon Rhim, Eu Young Jae, Ju Yeon Lee, Chul Won Lee, Hyun Ho Jung, Jae Young Seong, Seungkyu Lee, Ha Hyung Kim |
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| Rok vydání: | 2009 |
| Předmět: |
Agonist
Models Molecular medicine.drug_class Biophysics Biochemistry Micelle Protein Structure Secondary Turn (biochemistry) chemistry.chemical_compound Membrane Lipids Kisspeptin Amide medicine Animals Lipid bilayer Molecular Biology Nuclear Magnetic Resonance Biomolecular DNA Primers Kisspeptins Base Sequence Circular Dichroism Proteins Ligand (biochemistry) Rats Membrane chemistry hormones hormone substitutes and hormone antagonists |
| Zdroj: | Archives of biochemistry and biophysics. 485(2) |
| ISSN: | 1096-0384 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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