Amyloids adopt ‘cross-β’ structures composed of long, twisted fibrils with β-strands running perpendicular to the fibril axis. Recently, a toxic peptide was proposed to form amyloid-like cross-α structures in solution, with a planar bilayer-like assembly observed in the crystal structure. Here we crystallographically characterize designed peptides that assemble into spiraling cross-α amyloid-like structures, which resemble twisted β-amyloid fibrils. The peptides form helical dimers, stabilized by packing of small and apolar residues, and the dimers further assemble into cross-α amyloid-like fibrils with superhelical pitches ranging from 170 Å to 200 Å. When a small residue that appeared critical for packing was converted to leucine, it resulted in structural rearrangement to a helical polymer. Fluorescently tagged versions of the designed peptides form puncta in mammalian cells, which recover from photobleaching with markedly different kinetics. These structural folds could be potentially useful for directing in vivo protein assemblies with predetermined spacing and stabilities.

淀粉样蛋白采用“交叉-β”结构，该结构由扭曲的长原纤维构成，β链垂直于原纤维轴延伸。最近，有人提出了一种有毒的肽在溶液中形成淀粉样样的交叉α结构，并在晶体结构中观察到平面双层样的组装。在这里，我们对设计的肽进行晶体学表征，这些肽装配成螺旋形的交叉α-淀粉样结构，类似于扭曲的β-淀粉样原纤维。肽形成螺旋二聚体，通过小的和非极性残基的堆积而稳定，并且二聚体进一步组装成交叉α淀粉样蛋白原纤维，超螺旋间距在170到200范围内。当对包装至关重要的少量残留物转化为亮氨酸时，会导致结构重排成螺旋状聚合物。设计的肽的荧光标记版本在哺乳动物细胞中形成点状，可从光漂白中恢复，并具有明显不同的动力学。这些结构折叠对于指导具有预定间隔和稳定性的体内蛋白质组装可能是有用的。