Structures and Dynamics of Anionic Lipoprotein Nanodiscs.
Structures and Dynamics of Anionic Lipoprotein Nanodiscs.
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DOI：
10.1021/acs.jpcb.2c00758
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发表时间：
2022-04-21
影响因子：
3.3
通讯作者：
Hackett, John C.
中科院分区：
文献类型：
--
作者：
Sweeney, D. Tyler;Krueger, Susan;Sen, Kakali;Hackett, John C.
被称为纳米圆盘 (ND) 的纳米脂蛋白颗粒已成为稳定膜蛋白的多功能且强大的工具，允许进行大量的结构和生物物理研究。它们的部分吸引力在于它们能够灵活地适应多种类型的脂质，并且能够精确控制成分。然而，人们对脂质成分的变化如何影响其结构和动力学知之甚少。在此，我们研究了将阴离子脂质 POPG 引入 POPC ND 中如何影响这些特性。可变成分 ND 的小角 X 射线和中子散射（SAXS 和 SANS）与分子动力学模拟相辅相成，以探讨增加 POPG 的关注如何影响 ND 形状、脂质核心结构以及流行的膜支架蛋白 MSP1D1(−) 的动力学。包含 POPG 的一个便利好处是，它消除了在纯 POPC ND 中观察到的 D2O 诱导的聚集，从而允许 SANS 在多种对比下进行研究。 SAXS 和 SANS 数据可以全局拟合堆叠椭圆柱模型以及考虑膜曲率的模型的扩展。对这两个模型的拟合支持 POPG 的引入导致强椭圆 ND；然而，MD 模拟预测了膜的曲率，从而支持后一种模型的使用。与模型无关的参数的趋势表明，POPG 的增加降低了 MSP1D1(−) 的构象异质性，这与 MD 模拟一致，MD 模拟显示，掺入足够的 POPG 会抑制 N 端螺旋与脂质核心的脱离。这些研究强调了 ND 响应阴离子脂质的新结构变化，并将为未来嵌入混合脂质成分 ND 中的膜蛋白结构研究的解释提供信息。
Nanolipoprotein particles known as nanodiscs (NDs) have emerged as versatile and powerful tools for the stabilization of membrane proteins permitting a plethora of structural and biophysical studies. Part of their allure is their flexibility to accommodate many types of lipids and precise control of the composition. However, little is known about how variations in lipid composition impact their structures and dynamics. Herein, we investigate how the introduction of the anionic lipid POPG into POPC NDs impacts these features. Small-angle X-ray and neutron scattering (SAXS and SANS) of variable-composition NDs are complemented with molecular dynamics simulations to interrogate how increasing the concern of POPG impacts the ND shape, structure of the lipid core, and the dynamics of the popular membrane scaffold protein, MSP1D1(−). A convenient benefit of including POPG is that it eliminates D2O-induced aggregation observed in pure POPC NDs, permitting studies by SANS at multiple contrasts. SAXS and SANS data could be globally fit to a stacked elliptical cylinder model as well as an extension of the model that accounts for membrane curvature. Fitting to both models supports that the introduction of POPG results in strongly elliptical NDs; however, MD simulations predict the curvature of the membrane, thereby supporting the use of the latter model. Trends in the model-independent parameters suggest that increases in POPG reduce the conformational heterogeneity of the MSP1D1(−), which is in agreement with MD simulations that show that the incorporation of sufficient POPG suppresses disengagement of the N-terminal helix from the lipid core. These studies highlight novel structural changes in NDs in response to an anionic lipid and will inform the interpretation of future structural studies of membrane proteins embedded in NDs of mixed lipid composition.
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影响因子：
3.5
作者：
Gapsys, Vytautas;de Groot, Bert L.;Briones, Rodolfo
通讯作者：
Briones, Rodolfo
DOI：
10.1007/978-1-62703-691-7_18
发表时间：
2014
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Dyer, Kevin N;Hammel, Michal;Rambo, Robert P;Tsutakawa, Susan E;Rodic, Ivan;Classen, Scott;Tainer, John A;Hura, Greg L
通讯作者：
Hura, Greg L
影响因子：
3.4
作者：
Pan, Jianjun;Heberle, Frederick A.;Tristram-Nagle, Stephanie;Szymanski, Michelle;Koepfinger, Mary;Katsaras, John;Kucerka, Norbert
通讯作者：
Kucerka, Norbert
影响因子：
2.5
作者：
Classen S;Rodic I;Holton J;Hura GL;Hammel M;Tainer JA
通讯作者：
Tainer JA
影响因子：
15
作者：
Nakano, Minoru;Fukuda, Masakazu;Handa, Tetsurou
通讯作者：
Handa, Tetsurou