Conservation of Complex Knotting and Slipknotting Patterns in Proteins

Abstract

The last decade has shown that there are an increasing numbers of known proteins that contain linear open knots or slipknots in their native folded structure. In general, knots in proteins are orders of magnitude less frequent than would be expected for random polymers with similar length, compactness, and flexibility. Explaining why they are so rare is an intriguing question. While analyzing all available protein structures for the presence of knots and slipknots we detected a surprising conservation of complex knotting patterns within and between several protein families despite their large sequence divergence. Since protein folding pathways leading to knotted native protein structures are slower and less efficient than those leading to unknotted proteins with similar size and sequence, the strict conservation of the knotting pattern in some families of proteins indicates an important physiological role of knots and slipknots in these proteins. Although little is known about the functional role of knots, recent studies have demonstrated a protein-stabilizing ability of knots and slipknots. In the slipknots studied here, some of the conserved knotting patterns occur in transmembrane domains of proteins, suggesting that slipknots may stabilize these domains against forces acting during their translocation through protein lined membrane pores.