Membrane-induced tau amyloid fibrils.
Membrane-induced tau amyloid fibrils.
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DOI：
10.1038/s42003-023-04847-6
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发表时间：
2023-04-28
影响因子：
5.9
通讯作者：
Hong, Mei
中科院分区：
文献类型：
--
作者：
Mammeri, Nadia El;Gampp, Olivia;Duan, Pu;Hong, Mei
固有的蛋白质tau聚集到β-折叠的淀粉样蛋白纤维中，这些淀粉样蛋白在与阿尔茨海默氏病和其他神经退行性疾病相互作用的人的大脑中，与脂质膜相互作用。 tau构造微管结合重复和富含脯氨酸的结构域被重构为含胆固醇的磷脂膜，表明TAU在几周内从随机线圈转化为β-片蔬菜的β-含量差异。重要的是，SUV结合的tau产生了长长的原纤维，暴露了特征性的β-在肝素 - 纤维中的Tyr310相比，LUV和MLV会引起纤维，但会引起不同的β-折叠聚集体。 ，表明膜曲率和胆固醇都是Tau原纤维形成所需的结果。
固态NMR和TEM揭示了与脂质膜相互作用时Tau蛋白构象，动力学和形态的时间依赖性变化，例如SUV，LUVS和MLV与不同脂质组合物的MLV。
The intrinsically disordered protein tau aggregates into β-sheet amyloid fibrils that spread in human brains afflicted with Alzheimer’s disease and other neurodegenerative diseases. Tau interaction with lipid membranes might play a role in the formation and spreading of these pathological aggregates. Here we investigate the conformation and assembly of membrane-induced tau aggregates using solid-state NMR and transmission electron microscopy. A tau construct that encompasses the microtubule-binding repeats and a proline-rich domain is reconstituted into cholesterol-containing phospholipid membranes. 2D 13C-13C correlation spectra indicate that tau converted from a random coil to a β-sheet conformation over weeks. Small unilamellar vesicles (SUVs) cause different equilibrium conformations from large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). Importantly, SUV-bound tau developed long fibrils that exhibit the characteristic β-sheet chemical shifts of Tyr310 in heparin-fibrillized tau. In comparison, LUVs and MLVs do not induce fibrils but cause different β-sheet aggregates. Lipid-protein correlation spectra indicate that these tau aggregates reside at the membrane-water interface, without inserting into the middle of the lipid bilayer. Removal of cholesterol from the SUVs abolished the fibrils, indicating that both membrane curvature and cholesterol are required for tau fibril formation. These results have implications for how lipid membranes might nucleate tau aggregates. Solid-state NMR and TEM reveal time-dependent changes in the conformation, dynamics, and morphology of the tau protein upon interactions with lipid membranes, such as SUVs, LUVs, and MLVs with different lipid compositions.
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影响因子：
4.3
作者：
DeVos SL;Corjuc BT;Oakley DH;Nobuhara CK;Bannon RN;Chase A;Commins C;Gonzalez JA;Dooley PM;Frosch MP;Hyman BT
通讯作者：
Hyman BT
影响因子：
16.6
作者：
Chakraborty P;Rivière G;Liu S;de Opakua AI;Dervişoğlu R;Hebestreit A;Andreas LB;Vorberg IM;Zweckstetter M
通讯作者：
Zweckstetter M
影响因子：
3.7
作者：
Dujardin S;Bégard S;Caillierez R;Lachaud C;Delattre L;Carrier S;Loyens A;Galas MC;Bousset L;Melki R;Aurégan G;Hantraye P;Brouillet E;Buée L;Colin M
通讯作者：
Colin M
影响因子：
15
作者：
Daebel, Venita;Chinnathambi, Subashchandrabose;Lange, Adam
通讯作者：
Lange, Adam
影响因子：
1.7
作者：
Baldus, M;Petkova, AT;Griffin, RG
通讯作者：
Griffin, RG