title: Headgroup-dependent membrane catalysis of apelin-receptor interactions is likely.
abstract: Apelin is the peptidic ligand for the G-protein-coupled receptor APJ. The apelin-APJ system is important in cardiovascular regulation, fluid homeostasis, and angiogenesis, among other roles. In this study, we investigate interactions between apelin and membrane-mimetic micelles of the detergents sodium dodecyl sulfate (SDS), dodecylphosphocholine (DPC), and 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] (LPPG). Far-ultraviolet circular dichroism spectropolarimetry and diffusion-ordered spectroscopy indicate that apelin peptides bind to micelles of the anionic detergents SDS and LPPG much more favorably than to zwitterionic DPC micelles. Nuclear magnetic resonance spectroscopy allowed full characterization of the interactions of apelin-17 with SDS micelles. Titration with paramagnetic agents and structural determination of apelin-17 in SDS indicate that R6-K12 is highly structured, with R6-L9 directly interacting with headgroups of the micelle. Type I beta-turns are initiated between R6 and L9, and a well-defined type IV beta-turn is initiated at S10. Furthermore, binding of apelin-17 to SDS micelles causes structuring of M15-F17, with no evidence for direct binding of this region to the micelles. These results are placed into the context of the membrane catalysis hypothesis for peptide-receptor binding, and a hypothetical mechanism of APJ binding and activation by apelin is advanced.
authors.affiliation: Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
authors.forename: David N
authors.initials: DN
authors.lastname: Langelaan
authors.forename: Jan K
authors.initials: JK
authors.lastname: Rainey
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D002462:Cell Membrane / Q000378:metabolism*; D002942:Circular Dichroism; D004058:Diffusion; D006017:Glycolipids / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D008823:Micelles; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000378:metabolism; D017186:Titrimetry
chemical_list: D006017:Glycolipids; D007295:Inositol Phosphates; D036341:Intercellular Signaling Peptides and Proteins; C111513:LPPG glycoinositolphosphoceramide; D008823:Micelles; D043562:Receptors, G-Protein-Coupled; C495200:apelin-12 peptide; D010767:Phosphorylcholine; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine