Department of Biology and Chemistry, Paul Scherrer Institute, 5232, Villigen, Switzerland.
Angew Chem Int Ed Engl. 2023 Jun 5;62(23):e202216480. doi: 10.1002/anie.202216480. Epub 2023 Apr 12.
Prevalent in nature, protein oligomers play critical roles both physiologically and pathologically. The multimeric nature and conformational transiency of protein oligomers greatly complicate a more detailed glimpse into the molecular structure as well as function. In this minireview, the oligomers are classified and described on the basis of biological function, toxicity, and application. We also define the bottlenecks in recent oligomer studies and further review numerous frontier methods for engineering protein oligomers. Progress is being made on many fronts for a wide variety of applications, and protein grafting is highlighted as a promising and robust method for oligomer engineering. These advances collectively allow the engineering and design of stabilized oligomers that bring us one step closer to understanding their biological functions, toxicity, and a wide range of applications.
在自然界中普遍存在的蛋白质寡聚体在生理和病理上都起着关键作用。蛋白质寡聚体的多聚体性质和构象瞬变极大地增加了对其分子结构和功能进行更详细观察的难度。在这篇简评中,我们根据生物功能、毒性和应用对寡聚体进行了分类和描述。我们还定义了最近寡聚体研究中的瓶颈,并进一步综述了用于工程化蛋白质寡聚体的众多前沿方法。在许多领域的应用中都取得了进展,蛋白质嫁接被作为一种很有前途和强大的寡聚体工程方法而被突出强调。这些进展共同使得稳定化寡聚体的工程化和设计成为可能,这使我们更接近于理解它们的生物学功能、毒性和广泛的应用。