[NMR paper] Nanodisc-targeted STD NMR reveals atomistic details of ligand binding to lipid environments.

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Nanodisc-targeted STD NMR reveals atomistic details of ligand binding to lipid environments.

Nanodisc-targeted STD NMR reveals atomistic details of ligand binding to lipid environments.

Chembiochem. 2018 Mar 14;:

Authors: Watts A

Abstract
Saturation transfer difference (STD) NMR constitutes 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 of 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, where 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 to investigate the interactions of the neurotransmitter dopamine to mimetics of lipid bilayers, such as nanodiscs, by saturation of the latter. In particular, the interactions between dopamine and model lipid nanodiscs formed from charged and zwitterionic lipids have been resolved at the atomic level. The results, in agreement with previous isothermal titration calorimetry (ITC) studies, show that dopamine preferential binds to negatively charged model membranes, but also provides detailed atomistic insights into the mode of interaction of dopamine to membrane mimetics. Our findings provide relevant structural information for the design of lipid-based drug carriers of dopamine, structural analogues, and are of generic applicability to other systems.


PMID: 29537625 [PubMed - as supplied by publisher]



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