In Search of Functional Advantages of Knots in Proteins

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.

Knotted proteins: Tie etiquette in structural biology

“…It has been proposed that knotted proteins have enhanced thermal (20,26), mechanical (26,27,128) and structural (127) stabilities. Another possibility is that knots help shape and stabilize the active site of enzyme (129)(130)(131), and in some cases it has even been suggested that knots can control enzymatic (130) and signaling activity (132). A recent study put forward the view that knots can impair protein degradation by ATP-dependent proteases leading to partially degraded products with potentially new functions (133).…”

Conserved architecture of Tc toxins from human and insect pathogenic bacteria

“…The main differences are mostly located at the RBDs (Figure 1a indicating that it does untangle during prepore-to-pore transition ( Figure 3b). A 31 trefoil protein knot is the most simple and common knot type 18 . It mostly occurs in smaller proteins or enzymes such as methyltransferases and carbonic anhydrases 19 .…”

“…With ~280 kDa (mass of Pl-TcdA1 monomer), TcA is, to our knowledge, by far the largest protein for which such a knot has been observed. The folding mechanism of a knotted protein has been shown to be quite complex and the folding rate of knotted proteins is decreased 18,20 . These findings suggest that it is rather surprising that the complex TcA structure contains a knot.…”

Untying the Photophysics of Quinolinium‐Based Molecular Knots and Links

“…[7][8][9] Several studies have highlighted the importance of naturallyo ccurring molecular knots. [10,11] Similarly,t he formation of knots in polymers is thought to result in unique thermal, mechanical and dynamical properties. [10,11] Similarly,t he formation of knots in polymers is thought to result in unique thermal, mechanical and dynamical properties.…”