|
|||||
|
|
Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy |
|
| Authors: | Roy A. M. van Beekveld Maik G. N. Derks Raj Kumar Leanna Smid Thorben Maass Dr. João Medeiros-Silva Dr. Eefjan Breukink Dr. Markus Weingarth |
| Affiliation: | 1. NMR Spectroscopy, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands These authors contributed equally to this work.;2. NMR Spectroscopy, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands These authors contributed equally to this work.;3. NMR Spectroscopy, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands;4. NMR Spectroscopy, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands Present address: Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, MA 02139 USA;5. Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands |
| Abstract: | Specific interactions with phospholipids are often critical for the function of proteins or drugs, but studying these interactions at high resolution remains difficult, especially in complex membranes that mimic biological conditions. In principle, molecular interactions with phospholipids could be directly probed by solid-state NMR (ssNMR). However, due to the challenge to detect specific lipids in mixed liposomes and limited spectral sensitivity, ssNMR studies of specific lipids in complex membranes are scarce. Here, by using purified biological 13C,15N-labeled phospholipids, we show that we can selectively detect traces of specific lipids in complex membranes. In combination with 1H-detected ssNMR, we show that our approach provides unprecedented high-resolution insights into the mechanisms of drugs that target specific lipids. This broadly applicable approach opens new opportunities for the molecular characterization of specific lipid interactions with proteins or drugs in complex fluid membranes. |
| Keywords: | antibiotics cinnamycin lipids membranes solid state NMR |