牛血清白蛋白聚集体的分解动力学

Structural insights into bovine serum albumin aggregates by a dissociation kinetic investigation

以牛血清白蛋白(BSA)作为模型蛋白,通过浊度法研究BSA形成的无序蛋白聚集体的分解动力学并揭示其复杂结构细节.实验发现,BSA无序聚集体在碱性条件下分解过程有4个动力学阶段,包括1个快速的分解阶段,2个相对较慢的分解阶段和1个动力学惰性阶段.由此推测BSA聚集体中至少含有4种不同的BSA单体形态.

Protein aggregation is not only a common problem in biopharmaceutical industry involving protein drugs, but also a devastating phenomenon closely linked to numerous human diseases. Under- standing structural details of protein aggregates is fundamentally important in the prediction and preven- tion of protein aggregation behavior. In this study, we explore to use a turbidity-based dissociation kinetic assay to tackle the complex nature of protein amorphous aggregates by a model protein, bovine serum al- bumin（BSA）. We observe that the dissociation of BSA aggregates under basic condition consists of four distinct kinetic phases, including a burst phase, two relatively slow phases, and one kinetically inert phase. Such kinetic observation allows us to hypothesize that BSA aggregates consist of at least four dif- ferent types of BSA monomeric structures at the molecular level. To the best of our knowledge, this is the first turbidity-based investigation with the aim to elucidate the structural heterogeneity of protein a- morphous aggregates.