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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.

SUBMITTER: Langelaan DN

PROVIDER: S-EPMC2736645 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Headgroup-dependent membrane catalysis of apelin-receptor interactions is likely.

Langelaan David N DN Rainey Jan K JK

The journal of physical chemistry. B 20090701 30

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-or ...[more]

PMID: 19708686

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Project description:Ceramide is a major actor in the sphingolipid signaling pathway elicited by various kinds of cell stress. Under those conditions ceramide (Cer) is produced in the plasma membrane as a product of sphingomyelin (SM) hydrolysis, and this may lead to apoptosis. Thus, SM and Cer coexist in the membrane for some time, and they are known to separate laterally from the (more abundant) glycerolipids, giving rise to highly rigid domains or platforms. The properties of these domains/platforms are rather well understood, but the underlying SM:Cer molecular interactions have not been explored in detail. Infrared (IR) spectroscopy is a powerful analytical technique that provides information on all the chemical groupings in a molecule, and that can be applied to membranes and lipid bilayers in aqueous media. IR spectra can be conveniently retrieved as a function of temperature, thus revealing the thermotropic transitions of SM and its mixtures with Cer. Four regions of the IR spectrum of these sphingolipids have been examined, two of them dominated by the hydrophobic regions in the molecules, namely the C-H stretching vibrations (2800-3000 cm-1), and the CH2 scissoring vibrations (1455-1485 cm-1), and two others arising from chemical groups at the lipid-water interface, the sphingolipid amide I band (1600-1680 cm-1), and the phosphate vibrations in the 1000-1110 cm-1 region. The latter two regions have been rarely studied in the past. The IR data from the hydrophobic components show a gel (or ripple)-fluid transition of SM at 40 °C, that is shifted up to about 70 °C when Cer is added to the bilayers, in agreement with previous studies using a variety of techniques. IR information concerning the polar parts is more interesting. The amide I (carbonyl) band of pure SM exhibits a maximum at 1638 cm-1 at room temperature, and its position is shifted by about 10 cm-1 in the presence of Cer. Cer causes also a change in the overall band shape, but no signs of band splitting are seen, suggesting that SM and Cer carbonyl groups are interacting tightly, presumably through H-bonds. The 1086 cm-1 band, corresponding to PO2- vibrations, appears more stable in SM than in DPPC, and it is further stabilized by Cer, again suggesting an important role of H-bonds in the formation of SM:Cer clusters. Thus, SM and Cer can interact through their polar headgroups, in a way that is not accessible to other lipid classes.

Dataset Information

Headgroup-dependent membrane catalysis of apelin-receptor interactions is likely.

Publications

Headgroup-dependent membrane catalysis of apelin-receptor interactions is likely.

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