Half-turns are shown to be the main determinants of many experimental Alzheimer’s Aβ fibril structures. Fibril structures contain three half-turn types, βα_Rβ, βα_Lβ and βεβ which each result in a ∼90° bend in a β-strand. It is shown that only these half-turns enable cross-β stacking and thus the right-angle fold seen in fibrils is an intrinsic feature of cross-β. Encoding a strand as a conformational sequence in β, α_R, α_L and ε(β_L), pairwise combination rules for consecutive half-turns are used to decode this sequence to give the backbone path. This reveals how structures would be dramatically affected by a deletion. Using a wild-type Aβ(42) fibril structure and the pairwise combination rules, the Osaka deletion is predicted to result in exposure of surfaces that are mutually shielding from the solvent. Molecular dynamics simulations on an 11-mer β-sheet of Alzheimer’s Aβ(40) of the Dutch (E22Q), Iowa (D23N), Arctic (E22G), and Osaka (E22Δ) mutants, show the crucial role glycine plays in the positioning of βα_Rβ half-turns. Their “in-phase” positions along the sequence in the wild-type, Dutch mutant and Iowa mutant means that the half-folds all fold to the same side creating the same closed structure. Their out-of-phase positions in Arctic and Osaka mutants creates a flatter structure in the former and an S-shape structure in the latter which, as predicted, exposes surfaces on the inside in the closed wild-type to the outside. This is consistent with the gain of interaction model and indicates how domain swapping might explain the Osaka mutant’s unique properties.

半匝被证明是许多实验性阿尔茨海默氏症 Aβ 原纤维结构的主要决定因素。原纤维结构包含三种半转角类型，βα _R β、 βα _L β 和 βεβ，它们各自导致 β 链中的 ∼90° 弯曲。结果表明，只有这些半圈才能实现交叉β堆叠，因此在原纤维中看到的直角折叠是交叉β的内在特征。将一条链编码为 β、αR _、 αL_和ε(βL _{)中的构象序列})，连续半圈的成对组合规则用于解码该序列以给出主干路径。这揭示了结构将如何受到删除的显着影响。使用野生型 Aβ(42) 原纤维结构和成对组合规则，预计大阪缺失会导致相互屏蔽溶剂的表面暴露。对荷兰 (E22Q)、爱荷华州 (D23N)、北极 (E22G) 和大阪 (E22Δ) 突变体的阿尔茨海默病 Aβ(40) 的 11 聚体 β-折叠进行分子动力学模拟，显示甘氨酸在定位中的关键作用βαR _{_}β半圈。它们在野生型、荷兰突变体和爱荷华突变体中沿序列的“同相”位置意味着半折叠都折叠到同一侧，形成相同的封闭结构。它们在北极和大阪突变体中的异相位置在前者中产生了更平坦的结构，在后者中产生了 S 形结构，正如预测的那样，将封闭野生型的内部表面暴露在外部。这与交互模型的增益一致，并表明域交换如何解释大阪突变体的独特特性。