Abstract

While analyzing all available protein structures for the presence of knots and slipknots we detected a strict 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 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. Some of the conserved knotting patterns occur in proteins forming transmembrane channels where the slipknot loop seems to strap together the transmembrane helices forming the channel. This is joint work with Ken Millett, Andrzej Stasiak and Jose Onuchic.