Folding and functions of knotted proteins

Abstract

Topologically knotted proteins have entangled structural elements within their native structures that cannot be disentangled simply by pulling from the N- and C-termini. Systematic surveys have identified different types of knotted protein structures, constituting as much as 1% of the total entries within the Protein Data Bank. Many knotted proteins rely on their knotted structural elements to carry out evolutionarily conserved biological functions. Being knotted may also provide mechanical stability to withstand unfolding-coupled proteolysis. Reconfiguring a knotted protein topology by circular permutation or cyclization provides insights into the importance of being knotted in the context of folding and functions. With the explosion of predicted protein structures by artificial intelligence, we are now entering a new era of exploring the entangled protein universe.