Nanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environments

Saturation transfer difference (STD) NMR spectroscopy is one of the most popular ligand‐based NMR techniques for the study of protein–ligand interactions. This is due to its robustness and the fact that it is focused on the signals of the ligand, without any need for NMR information on the macromole...

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Main Authors: Muñoz‐García, J, Inacio dos Reis, R, Taylor, R, Henry, A, Watts, A
Format: Journal article
Language:English
Published: Wiley 2018
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author Muñoz‐García, J
Inacio dos Reis, R
Taylor, R
Henry, A
Watts, A
author_facet Muñoz‐García, J
Inacio dos Reis, R
Taylor, R
Henry, A
Watts, A
author_sort Muñoz‐García, J
collection OXFORD
description Saturation transfer difference (STD) NMR spectroscopy is one of the most popular ligand‐based NMR techniques for the study of protein–ligand interactions. This is due to its robustness and the fact that it is focused on the signals of the ligand, without any need for NMR information on the macromolecular target. This technique is most commonly applied to systems involving different types of ligands (e.g., small organic molecules, carbohydrates or lipids) and a protein as the target, in which the latter is selectively saturated. However, only a few examples have been reported where membrane mimetics are the macromolecular binding partners. Here, we have employed STD NMR spectroscopy to investigate the interactions of the neurotransmitter dopamine with mimetics of lipid bilayers, such as nanodiscs, by saturation of the latter. In particular, the interactions between dopamine and model lipid nanodiscs formed either from charged or zwitterionic lipids have been resolved at the atomic level. The results, in agreement with previous isothermal titration calorimetry studies, show that dopamine preferentially binds to negatively charged model membranes, but also provide detailed atomic insights into the mode of interaction of dopamine with membrane mimetics. Our findings provide relevant structural information for the design of lipid‐based drug carriers of dopamine and its structural analogues and are of general applicability to other systems.
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spelling oxford-uuid:c7a95cf5-7656-4629-9bb2-179d7c4167462022-03-27T06:46:40ZNanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environmentsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c7a95cf5-7656-4629-9bb2-179d7c416746EnglishSymplectic Elements at OxfordWiley2018Muñoz‐García, JInacio dos Reis, RTaylor, RHenry, AWatts, ASaturation transfer difference (STD) NMR spectroscopy is one of the most popular ligand‐based NMR techniques for the study of protein–ligand interactions. This is due to its robustness and the fact that it is focused on the signals of the ligand, without any need for NMR information on the macromolecular target. This technique is most commonly applied to systems involving different types of ligands (e.g., small organic molecules, carbohydrates or lipids) and a protein as the target, in which the latter is selectively saturated. However, only a few examples have been reported where membrane mimetics are the macromolecular binding partners. Here, we have employed STD NMR spectroscopy to investigate the interactions of the neurotransmitter dopamine with mimetics of lipid bilayers, such as nanodiscs, by saturation of the latter. In particular, the interactions between dopamine and model lipid nanodiscs formed either from charged or zwitterionic lipids have been resolved at the atomic level. The results, in agreement with previous isothermal titration calorimetry studies, show that dopamine preferentially binds to negatively charged model membranes, but also provide detailed atomic insights into the mode of interaction of dopamine with membrane mimetics. Our findings provide relevant structural information for the design of lipid‐based drug carriers of dopamine and its structural analogues and are of general applicability to other systems.
spellingShingle Muñoz‐García, J
Inacio dos Reis, R
Taylor, R
Henry, A
Watts, A
Nanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environments
title Nanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environments
title_full Nanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environments
title_fullStr Nanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environments
title_full_unstemmed Nanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environments
title_short Nanodisc‐targeted STD NMR spectroscopy reveals atomic details of ligand binding to lipid environments
title_sort nanodisc targeted std nmr spectroscopy reveals atomic details of ligand binding to lipid environments
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AT taylorr nanodisctargetedstdnmrspectroscopyrevealsatomicdetailsofligandbindingtolipidenvironments
AT henrya nanodisctargetedstdnmrspectroscopyrevealsatomicdetailsofligandbindingtolipidenvironments
AT wattsa nanodisctargetedstdnmrspectroscopyrevealsatomicdetailsofligandbindingtolipidenvironments