Antimicrobial activity is being increasingly linked to amyloid fibril formation, suggesting physiological roles for some human amyloids, which have historically been viewed as strictly pathological agents. This work reports on formation of functional cross-α amyloid fibrils of the amphibian antimicrobial peptide uperin 3.5 at atomic-resolution, an architecture initially discovered in the bacterial PSMα3 cytotoxin. The fibrils of uperin 3.5 and PSMα3 were comprised of parallel and anti-parallel helical sheets, respectively, recapitulating properties of β-sheets. Uperin 3.5 helical fibril formation was largely induced by, and formed on, bacterial cells or membrane mimetics, and led to membrane damage and cell death. Uperin 3.5 demonstrated chameleon properties, with a secondary structure switch to cross-β fibrils with reduced antibacterial activity in the absence of lipids or after heat shock. These findings suggest a regulation mechanism, which includes storage of inactive peptides as well as environmentally induced activation of uperin 3.5, via chameleon cross-α/β amyloid fibrils.

中文翻译：

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两栖类抗菌肽Uperin 3.5是一种跨α/跨β变色龙功能性淀粉样蛋白

抗菌活性正越来越多地与淀粉样蛋白原纤维形成联系起来，表明某些人类淀粉样蛋白的生理作用，这些淀粉样蛋白在历史上一直被视为严格的病理学因子。这项工作报告了在原子分辨率下两栖抗菌肽uperin 3.5的功能性交叉α淀粉样原纤维的形成，这种结构最初是在细菌PSMα3细胞毒素中发现的。Uperin 3.5和PSMα3的原纤维分别由平行和反平行的螺旋片组成，概括了β-片的性质。Uperin 3.5螺旋原纤维的形成主要由细菌细胞或膜模拟物诱导并形成于其上，并导致膜损伤和细胞死亡。Uperin 3.5展示了变色龙特性，在没有脂质或热休克后，具有二级结构的产品会转变为抗菌活性降低的交叉β原纤维。这些发现提示了一种调节机制，包括通过变色龙交叉α/β淀粉样蛋白原纤维存储非活性肽以及环境诱导的uperin 3.5活化。