Oh Hyeok Jin, Jung Yongwon
Department of Chemistry, KAIST 291 Daehak-ro, Yuseong-gu Daejeon 34141 Republic of Korea
Chem Sci. 2022 Dec 30;14(5):1105-1113. doi: 10.1039/d2sc02772k. eCollection 2023 Feb 1.
Protein cages are attractive building blocks to build high order materials such as 3D cage lattices, which offer accurately ordered bio-templates. However, controlling the size or valency of these cage-to-cage assemblies is extremely difficult due to highly multivalent and symmetric cage structures. Here, various high order cage assemblies with homogeneous sizes and geometries are constructed by developing an anisotropic ferritin cage with limitedly exposed binding modules, leucine zipper. The anisotropic ferritin is produced as expressed in cells without the need of complex cage fabrication by careful subunit manipulation. Ferritin cages with limitedly exposed zippers are assembled around a core ferritin with fully exposed opposing zippers, generating homogeneous high order structures, whereas two fully exposed ferritins are assembled into heterogeneous cage aggregates. Diverse fully exposed core cages are prepared by varying the zipper-ferritin fusion geometries and even by using larger cage structures. With these core cages and the anisotropic ferritin, a range of high order cage assemblies with diverse ferritin valencies (3 to over 12) and sizes (over 40 nm) are created. Cell surface binding and internalization of cage structures are greatly varied by assembly sizes, where high order ferritins are clearly more effective than monomeric ferritin.
蛋白质笼是构建高阶材料（如3D笼状晶格）的有吸引力的构建模块，这些高阶材料提供了精确有序的生物模板。然而，由于笼状结构具有高度多价和对称性，控制这些笼与笼组装体的大小或价态极其困难。在此，通过开发一种具有有限暴露结合模块（亮氨酸拉链）的各向异性铁蛋白笼，构建了各种具有均匀尺寸和几何形状的高阶笼组装体。各向异性铁蛋白在细胞中表达产生，无需通过仔细的亚基操作进行复杂的笼制备。具有有限暴露拉链的铁蛋白笼围绕着一个具有完全暴露的相对拉链的核心铁蛋白组装，形成均匀的高阶结构，而两个完全暴露的铁蛋白则组装成异质的笼聚集体。通过改变拉链 - 铁蛋白融合几何形状，甚至使用更大的笼状结构，可以制备各种完全暴露的核心笼。利用这些核心笼和各向异性铁蛋白，创建了一系列具有不同铁蛋白价态（3至超过12）和尺寸（超过40纳米）的高阶笼组装体。笼结构在细胞表面的结合和内化因组装大小而有很大差异，其中高阶铁蛋白明显比单体铁蛋白更有效。
