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Protein Oligomer Engineering: A New Frontier for Studying Protein Structure, Function, and Toxicity

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WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202216480

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Amyloid Proteins; Oligomers; Protein Engineering; Protein Functions; Protein Structures

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Protein oligomers are abundant in nature and have important roles in physiology and pathology. Their complex structure and conformational changes make it difficult to study them in detail. This article classifies and describes oligomers based on biological function, toxicity, and application. It also reviews recent advancements and methods for engineering protein oligomers, highlighting protein grafting as a promising approach. These developments bring us closer to understanding the biological functions, toxicity, and potential applications of stabilized oligomers.
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.

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