Conn Charlotte E, de Campo Liliana, Whitten Andrew E, Garvey Christopher J, Krause-Heuer Anwen M, van 't Hag Leonie
School of Science, STEM College, RMIT University, Melbourne, VIC, Australia.
Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia.
Front Chem. 2021 Feb 9;8:619470. doi: 10.3389/fchem.2020.619470. eCollection 2020.
This perspective describes advances in determining membrane protein structures in lipid bilayers using small-angle neutron scattering (SANS). Differentially labeled detergents with a homogeneous scattering length density facilitate contrast matching of detergent micelles; this has previously been used successfully to obtain the structures of membrane proteins. However, detergent micelles do not mimic the lipid bilayer environment of the cell membrane . Deuterated vesicles can be used to obtain the radius of gyration of membrane proteins, but protein-protein interference effects within the vesicles severely limits this method such that the protein structure cannot be modeled. We show herein that different membrane protein conformations can be distinguished within the lipid bilayer of the bicontinuous cubic phase using contrast-matching. Time-resolved studies performed using SANS illustrate the complex phase behavior in lyotropic liquid crystalline systems and emphasize the importance of this development. We believe that studying membrane protein structures and phase behavior in contrast-matched lipid bilayers will advance both biological and pharmaceutical applications of membrane-associated proteins, biosensors and food science.
这篇综述介绍了利用小角中子散射（SANS）测定脂质双层中膜蛋白结构的进展。具有均匀散射长度密度的差异标记去污剂有助于去污剂胶束的对比匹配；此前已成功用于获得膜蛋白的结构。然而，去污剂胶束无法模拟细胞膜的脂质双层环境。氘代囊泡可用于获得膜蛋白的旋转半径，但囊泡内的蛋白质-蛋白质干扰效应严重限制了该方法，以至于无法对蛋白质结构进行建模。我们在此表明，利用对比匹配可在双连续立方相的脂质双层中区分不同的膜蛋白构象。使用SANS进行的时间分辨研究阐明了溶致液晶系统中的复杂相行为，并强调了这一进展的重要性。我们认为，研究对比匹配脂质双层中的膜蛋白结构和相行为将推动膜相关蛋白、生物传感器和食品科学在生物学和制药领域的应用。
