Song Junyi, Liu Chuanyang, Li Baoshan, Liu Liangcheng, Zeng Ling, Ye Zonghuang, Wu Wenjian, Zhu Lingyun, Hu Biru
Department of Biology and Chemistry, College of Science, National University of Defense Technology, Changsha, Hunan, China.
Front Bioeng Biotechnol. 2023 Feb 20;11:1062769. doi: 10.3389/fbioe.2023.1062769. eCollection 2023.
Proteins, as gifts from nature, provide structure, sequence, and function templates for designing biomaterials. As first reported here, one group of proteins called reflectins and derived peptides were found to present distinct intracellular distribution preferences. Taking their conserved motifs and flexible linkers as Lego bricks, a series of reflectin-derivates were designed and expressed in cells. The selective intracellular localization property leaned on an RMs (canonical conserved reflectin motifs)-replication-determined manner, suggesting that these linkers and motifs were constructional fragments and ready-to-use building blocks for synthetic design and construction. A precise spatiotemporal application demo was constructed in the work by integrating RL (as one representative of a synthetic peptide derived from RfA1) into the Tet-on system to effectively transport cargo peptides into nuclei at selective time points. Further, the intracellular localization of RfA1 derivatives was spatiotemporally controllable with a CRY2/CIB1 system. At last, the functional homogeneities of either motifs or linkers were verified, which made them standardized building blocks for synthetic biology. In summary, the work provides a modularized, orthotropic, and well-characterized synthetic-peptide warehouse for precisely regulating the nucleocytoplasmic localization of proteins.
蛋白质作为大自然的馈赠，为生物材料的设计提供了结构、序列和功能模板。如本文首次报道，一类名为反射蛋白和衍生肽的蛋白质呈现出独特的细胞内分布偏好。以其保守基序和柔性接头作为乐高积木，设计了一系列反射蛋白衍生物并在细胞中表达。细胞内选择性定位特性依赖于一种由RMs（典型保守反射蛋白基序）复制决定的方式，这表明这些接头和基序是合成设计和构建的结构片段和即用型构建模块。通过将RL（作为源自RfA1的合成肽的代表之一）整合到Tet-on系统中，在这项工作中构建了一个精确的时空应用演示，以便在选择性时间点有效地将货物肽转运到细胞核中。此外，利用CRY2/CIB1系统可对RfA1衍生物的细胞内定位进行时空控制。最后，验证了基序或接头的功能同质性，这使其成为合成生物学的标准化构建模块。总之，这项工作提供了一个模块化、正交性且特征明确的合成肽库，用于精确调节蛋白质的核质定位。
