Wang Ruidi, Li Jiayu, Li Xiumei, Guo Jin, Liu Junqiu, Li Hongbin
State Key Laboratory of Supramolecular Structure and Materials , College of Chemistry , Jilin University , Changchun 130012 , P. R. China.
Department of Chemistry , The University of British Columbia , Vancouver , BC V6T 1Z1 , Canada . Email:
Chem Sci. 2019 Aug 20;10(40):9277-9284. doi: 10.1039/c9sc02128k. eCollection 2019 Oct 28.
The giant muscle protein titin is the largest protein in cells and responsible for the passive elasticity of muscles. Titin, made of hundreds of individually folded globular domains, is a protein polymer with folded globular domains as its macromonomers. Due to titin's ultrahigh molecular weight, it has been challenging to engineer high molecular weight artificial protein polymers that mimic titin. Taking advantage of protein fragment reconstitution (PFR) of a small protein GB1, which can be reconstituted from its two split fragments G and G, here we report the development of an efficient, PFR-based supramolecular polymerization strategy to engineer protein polymers with ultrahigh molecular weight. We found that the engineered bifunctional protein macromonomers (G-macromonomer-G) can undergo supramolecular polymerization, in a way similar to condensation polymerization, the reconstitution of G and G to produce protein polymers with ultrahigh molecular weight (with an average molecular weight of 0.5 MDa). Such high molecular weight linear protein polymers closely mimic titin and provide protein polymer building blocks for the construction of biomaterials with improved physical and mechanical properties.
巨大的肌肉蛋白肌联蛋白是细胞中最大的蛋白质，负责肌肉的被动弹性。肌联蛋白由数百个单独折叠的球状结构域组成，是以折叠的球状结构域作为其大分子单体的蛋白质聚合物。由于肌联蛋白的超高分子量，设计模仿肌联蛋白的高分子量人工蛋白质聚合物一直具有挑战性。利用小蛋白GB1的蛋白质片段重构（PFR），它可以从其两个分裂片段G和G重构而来，在此我们报告了一种基于PFR的高效超分子聚合策略的开发，以设计超高分子量的蛋白质聚合物。我们发现，工程化的双功能蛋白质大分子单体（G-大分子单体-G）可以进行超分子聚合，类似于缩聚反应，通过G和G的重构产生超高分子量的蛋白质聚合物（平均分子量为0.5 MDa）。这种高分子量线性蛋白质聚合物紧密模仿肌联蛋白，并为构建具有改善物理和机械性能的生物材料提供蛋白质聚合物构建块。
