Francisco Mendoza-Hoffmann, Canyong Guo, Yanzhuo Song, Dandan Feng, Lingyun Yang, Kurt Wüthrich
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引用次数: 0
摘要
对于在正十二烷基-β-D-麦芽糖苷（DDM）/胆固醇半琥珀酸酯（CHS）混合胶束中重构的 A2A 腺苷受体（A2AAR）（一种 A 类 G 蛋白偶联受体（GPCR）），之前的 19F-NMR 研究揭示了存在多种同时填充的构象状态。在这里，我们研究了不同去垢剂十二烷基麦芽糖新戊二醇（LMNG）与 CHS 混合胶束以及脂质双分子层纳米盘对这些构象平衡的影响。在 DDM/CHS 和 LMNG/CHS 胶束中，局部不同亚态的数量明显不同，而在 LMNG/CHS 胶束中，A2AAR 的构象流形与脂质双分子层纳米盘中的构象流形非常相似。考虑到纳米盘更接近天然脂质双分子层膜，这些观察结果表明 LMNG/CHS 胶束是在溶液中进行核磁共振研究的 A 类 GPCR 重组试验的良好选择。
19F-NMR studies of the impact of different detergents and nanodiscs on the A2A adenosine receptor
For the A2A adenosine receptor (A2AAR), a class A G-protein-coupled receptor (GPCR), reconstituted in n-dodecyl-β-D-maltoside (DDM)/cholesteryl hemisuccinate (CHS) mixed micelles, previous 19F-NMR studies revealed the presence of multiple simultaneously populated conformational states. Here, we study the influence of a different detergent, lauryl maltose neopentyl glycol (LMNG) in mixed micelles with CHS, and of lipid bilayer nanodiscs on these conformational equilibria. The populations of locally different substates are pronouncedly different in DDM/CHS and LMNG/CHS micelles, whereas the A2AAR conformational manifold in LMNG/CHS micelles is closely similar to that in the lipid bilayer nanodiscs. Considering that nanodiscs represent a closer match of the natural lipid bilayer membrane, these observations support that LMNG/CHS micelles are a good choice for reconstitution trials of class A GPCRs for NMR studies in solution.
期刊介绍：
The Journal of Biomolecular NMR provides a forum for publishing research on technical developments and innovative applications of nuclear magnetic resonance spectroscopy for the study of structure and dynamic properties of biopolymers in solution, liquid crystals, solids and mixed environments, e.g., attached to membranes. This may include:
Three-dimensional structure determination of biological macromolecules (polypeptides/proteins, DNA, RNA, oligosaccharides) by NMR.
New NMR techniques for studies of biological macromolecules.
Novel approaches to computer-aided automated analysis of multidimensional NMR spectra.
Computational methods for the structural interpretation of NMR data, including structure refinement.
Comparisons of structures determined by NMR with those obtained by other methods, e.g. by diffraction techniques with protein single crystals.
New techniques of sample preparation for NMR experiments (biosynthetic and chemical methods for isotope labeling, preparation of nutrients for biosynthetic isotope labeling, etc.). An NMR characterization of the products must be included.
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