AD-tau PHF与EGCG配合物的CryoEM结构。表没食子儿茶素没食子酸酯(EGCG)是绿茶中含量最多的多酚。它包括一个苯二醇环(a)与一个四氢吡喃部分(C)相连，这些环连接到一个没食子环(D)和邻苯三酚环(B)。8个羟基允许EGCG与许多生物分子进行氢键和其他极性相互作用。b EGCG孵育过程中脑源性phf的电子显微照片。在没有EGCG的情况下(上图)，观察到大量的原纤维(n = 15的代表性图像)。在37°C孵育3小时后(中间)，纤维形态出现细微变化，纤维模糊被膜变宽(n = 15的代表性图像)。在这个时间点看到的纤维要少得多。在EGCG孵育一夜后(下图)，罕见的剩余原纤维出现肿胀和干扰(代表性图像来自n = 8)。c添加EGCG前AD患者脑源性tau PHF cryoEM结构的横切面。d EGCG孵育3 h后Tau PHF结构。 Three new regions of density become apparent with the addition of EGCG (Sites 1–3). Site 1 is located in the polar cleft at the intersection of the two protofilaments composing the PHF. Sites 2 and 3 of new density are observed adjacent to K343 and K347 near the β-helix of the fibril. Both Sites 2 and 3 display weaker density than Site 1. e Tilted view of the 3-h structure with EGCG bound at Site 1. f Close up top- and side-views of EGCG in Site 1. This region borders N327, H329, E338, and K340 of the fibril, with EGCG making polar and hydrogen-bond contacts with these residues. EGCG adopts a primarily planar conformation when bound to the fibril, stabilized by π-π interactions of the stacked aromatic rings of EGCG. When viewed from the side of the fibril axis, the EGCG density is seen stacking with the same period as the fibril layers. g Side-view of a single EGCG molecule buried by the fibril and other copies of EGCG. Credit:自然通讯(2022)。DOI: 10.1038 / s41467 - 022 - 32951 - 4
