Folding and functions of knotted proteins

Area of Science:

• Biochemistry
• Structural Biology
• Protein Folding

Background:

• Topologically knotted proteins possess intrinsic entanglement within their native structures.
• These knotted structures are found in up to 1% of Protein Data Bank entries.
• Knotted elements are often essential for conserved biological functions and protein stability.

Purpose of the Study:

• To highlight the significance of topological knots in protein structure and function.
• To discuss the role of knots in protein mechanical stability and biological roles.
• To introduce the exploration of knotted proteins in the era of AI-predicted structures.

Main Methods:

• Systematic surveys of protein structures in the Protein Data Bank.
• Analysis of protein topology, including knotted structures.
• Investigation of protein reconfiguration through circular permutation and cyclization.

Main Results:

• Knotted protein structures are prevalent and functionally important.
• Protein knotting contributes to mechanical stability against proteolysis.
• Reconfiguring topology offers insights into the necessity of knots for folding and function.

Conclusions:

• Topological knots are integral to protein architecture and function.
• Understanding knotted proteins is crucial for structural biology and protein engineering.
• Artificial intelligence advancements are accelerating the exploration of the knotted protein landscape.