Biophysics, Faculty of Life Sciences, University of Copenhagen, DK-1165 Copenhagen, Denmark.
J Am Chem Soc. 2010 Oct 6;132(39):13713-22. doi: 10.1021/ja1030613.
Phospholipid bilayers host and support the function of membrane proteins and may be stabilized in disc-like nanostructures, allowing for unprecedented solution studies of the assembly, structure, and function of membrane proteins (Bayburt et al. Nano Lett. 2002, 2, 853-856). Based on small-angle neutron scattering in combination with variable-temperature studies of synchrotron small-angle X-ray scattering on nanodiscs in solution, we show that the fundamental nanodisc unit, consisting of a lipid bilayer surrounded by amphiphilic scaffold proteins, possesses intrinsically an elliptical shape. The temperature dependence of the curvature of the nanodiscs prepared with two different phospholipid types (DLPC and POPC) shows that it is the scaffold protein that determines the overall elliptical shape and that the nanodiscs become more circular with increasing temperature. Our data also show that the hydrophobic bilayer thickness is, to a large extent, dictated by the scaffolding protein and adjusted to minimize the hydrophobic mismatch between protein and phospholipid. Our conclusions result from a new comprehensive and molecular-based model of the nanodisc structure and the use of this to analyze the experimental scattering profile from nanodiscs. The model paves the way for future detailed structural studies of functional membrane proteins encapsulated in nanodiscs.
磷脂双层支持并承载着膜蛋白的功能，并且可能在盘状纳米结构中稳定存在，从而能够对膜蛋白的组装、结构和功能进行前所未有的溶液研究（Bayburt 等人，《Nano Lett.》2002 年，第 2 卷，853-856 页）。基于小角中子散射，并结合同步加速器小角 X 射线散射在溶液中对纳米盘的变温研究，我们表明，由双层磷脂和两亲性支架蛋白包围的基本纳米盘单元具有固有椭圆形形状。用两种不同的磷脂（DLPC 和 POPC）制备的纳米盘曲率的温度依赖性表明，是支架蛋白决定了整体椭圆形形状，并且纳米盘随温度升高变得更加圆形。我们的数据还表明，疏水双层的厚度在很大程度上由支架蛋白决定，并进行了调整以最小化蛋白和磷脂之间的疏水性不匹配。我们的结论源自纳米盘结构的新的全面的基于分子的模型，并使用该模型分析了来自纳米盘的实验散射分布。该模型为封装在纳米盘中的功能性膜蛋白的未来详细结构研究铺平了道路。
