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Engineering and functionalization of large circular tandem repeat protein nanoparticles.
Nature Structural & Molecular Biology ( IF 12.5 ) Pub Date : 2020-03-23 , DOI: 10.1038/s41594-020-0397-5
Colin E Correnti 1 , Jazmine P Hallinan 2 , Lindsey A Doyle 2 , Raymond O Ruff 1 , Carla A Jaeger-Ruckstuhl 1 , Yuexin Xu 1 , Betty W Shen 2 , Amanda Qu 2 , Caley Polkinghorn 3 , Della J Friend 2 , Ashok D Bandaranayake 1 , Stanley R Riddell 1 , Brett K Kaiser 3 , Barry L Stoddard 2 , Philip Bradley 1, 4
Affiliation  

Protein engineering has enabled the design of molecular scaffolds that display a wide variety of sizes, shapes, symmetries and subunit compositions. Symmetric protein-based nanoparticles that display multiple protein domains can exhibit enhanced functional properties due to increased avidity and improved solution behavior and stability. Here we describe the creation and characterization of a computationally designed circular tandem repeat protein (cTRP) composed of 24 identical repeated motifs, which can display a variety of functional protein domains (cargo) at defined positions around its periphery. We demonstrate that cTRP nanoparticles can self-assemble from smaller individual subunits, can be produced from prokaryotic and human expression platforms, can employ a variety of cargo attachment strategies and can be used for applications (such as T-cell culture and expansion) requiring high-avidity molecular interactions on the cell surface.



中文翻译:

大型圆形串联重复蛋白纳米颗粒的工程化和功能化。

蛋白质工程使分子支架的设计得以实现,这些分子支架具有各种尺寸,形状,对称性和亚基组成。由于增加的亲和力和改善的溶液行为和稳定性,显示多个蛋白质结构域的基于蛋白质的对称纳米颗粒可以表现出增强的功能特性。在这里,我们描述了由24个相同的重复基序组成的计算设计的圆形串联重复蛋白(cTRP)的创建和特征,该重复基序可以在其周边的指定位置显示各种功能蛋白结构域(货物)。我们证明了cTRP纳米颗粒可以从较小的单个亚基自我组装,可以从原核和人类表达平台中产生,

更新日期:2020-03-23
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