Abstract
We analysed the structure of deeply knotted proteins representing three unrelated families of knotted proteins. We looked at the correlation between positions of knotted cores in these proteins and such local structural characteristics as the number of intra-chain contacts, structural stability and solvent accessibility. We observed that the knotted cores and especially their borders showed strong enrichment in the number of contacts. These regions showed also increased thermal stability, whereas their solvent accessibility was decreased. Interestingly, the active sites within these knotted proteins preferentially located in the regions with increased number of contacts that also have increased thermal stability and decreased solvent accessibility. Our results suggest that knotting of polypeptide chains provides a favourable environment for the active sites observed in knotted proteins. Some knotted proteins have homologues without a knot. Interestingly, these unknotted homologues form local entanglements that retain structural characteristics of the knotted cores.
Highlights
Proteins belonging to several unrelated protein families fold towards their native structures in such a way that their polypeptide chains get tied into knots [1,2,3]
In our search of functional advantages of knots, we concentrate on proteins forming trefoil knots as these are the most frequently observed among knotted proteins
The knotted core is the smallest subchain of the entire polypeptide chain, which still forms the knot, while the tails are the parts of the chain remaining on both sides of the knotted core
Summary
Proteins belonging to several unrelated protein families fold towards their native structures in such a way that their polypeptide chains get tied into knots [1,2,3]. Most of them form simple trefoil knots, but there are proteins forming more complex knots such as figure-of-eight, pretzel-like pentaknot and Stevedore’s knot [1, 4,5,6]. It should be stressed here that these knots are not results of some accidental entanglements of long polypeptide chains but their complex structure and topology is entirely dictated by their sequence [7, 8]. Folding of knotted proteins is much slower and less efficient than of unknotted analogues [7,8,9]. The requirement to form a knot during folding provides evolutionary disadvantage. Several known families of knotted proteins have their knotted domains strongly conserved even in lines of organisms that got separated more than over a billion years ago [10]
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