Institute of Protein Biochemistry, Ulm University, 89081, Ulm, Germany.
Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.
Nat Commun. 2023 Jul 18;14(1):4293. doi: 10.1038/s41467-023-40042-1.
Amyloid fibrils have emerged as innovative tools to enhance the transduction efficiency of retroviral vectors in gene therapy strategies. In this study, we used cryo-electron microscopy to analyze the structure of a biotechnologically engineered peptide fibril that enhances retroviral infectivity. Our findings show that the peptide undergoes a time-dependent morphological maturation into polymorphic amyloid fibril structures. The fibrils consist of mated cross-β sheets that interact by the hydrophobic residues of the amphipathic fibril-forming peptide. The now available structural data help to explain the mechanism of retroviral infectivity enhancement, provide insights into the molecular plasticity of amyloid structures and illuminate the thermodynamic basis of their morphological maturation.
淀粉样纤维已成为增强逆转录病毒载体基因治疗策略转导效率的创新工具。在这项研究中，我们使用低温电子显微镜分析了一种生物技术工程化的肽纤维的结构，该纤维可增强逆转录病毒的感染力。我们的研究结果表明，该肽经历了时间依赖性的形态成熟，形成了多态淀粉样纤维结构。这些纤维由配对的交叉β片层组成，通过两亲性纤维形成肽的疏水性残基相互作用。现在可用的结构数据有助于解释逆转录病毒感染力增强的机制，深入了解淀粉样结构的分子可塑性，并阐明其形态成熟的热力学基础。
