Molecular interaction between kisspeptin decapeptide analogs and a lipid membrane.
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.
Lee
Ju Yeon
JY
Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Moon
Jung Sun
JS
Eu
Young-Jae
YJ
Lee
Chul Won
CW
Yang
Sung-Tae
ST
Lee
Seung Kyu
SK
Jung
Hyun Ho
HH
Kim
Ha Hyung
HH
Rhim
Hyewhon
H
Seong
Jae Young
JY
Kim
Jae Il
JI
D000818:Animals; D001483:Base Sequence; D002942:Circular Dichroism; D017931:DNA Primers; D059648:Kisspeptins; D008563:Membrane Lipids / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
D017931:DNA Primers; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D008563:Membrane Lipids; D011506:Proteins