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Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely

[Image: see text] 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...

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Autores principales: Langelaan, David N., Rainey, Jan K.
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2009
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736645/
https://www.ncbi.nlm.nih.gov/pubmed/19708686
http://dx.doi.org/10.1021/jp904562q
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author Langelaan, David N.
Rainey, Jan K.
author_facet Langelaan, David N.
Rainey, Jan K.
author_sort Langelaan, David N.
collection PubMed
description [Image: see text] 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 β-turns are initiated between R6 and L9, and a well-defined type IV β-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.
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spelling pubmed-27366452009-09-02 Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely Langelaan, David N. Rainey, Jan K. J Phys Chem B [Image: see text] 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 β-turns are initiated between R6 and L9, and a well-defined type IV β-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. American Chemical Society 2009-07-06 2009-07-30 /pmc/articles/PMC2736645/ /pubmed/19708686 http://dx.doi.org/10.1021/jp904562q Text en Copyright © 2009 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Langelaan, David N.
Rainey, Jan K.
Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely
title Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely
title_full Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely
title_fullStr Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely
title_full_unstemmed Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely
title_short Headgroup-Dependent Membrane Catalysis of Apelin−Receptor Interactions Is Likely
title_sort headgroup-dependent membrane catalysis of apelin−receptor interactions is likely
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736645/
https://www.ncbi.nlm.nih.gov/pubmed/19708686
http://dx.doi.org/10.1021/jp904562q
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