Novel Protein Topologies

Abstract

Are the polypeptide chains of native proteins ever tied into knots or links (catenated loops)? This question had been repeatedly addressed over the past 20 years [1–10], and it was, until recently, the general consensus that “linked loops and trefoil knots are not found in tertiary structure of proteins known to date” [7]. Typically, it was noted in 1993 that “True topological linking does not occur in any of the proteins currently represented in the PDB [Brookhaven Protein Data Bank] structure database” [8], that “The PDB structural database has been searched for knotted polypeptides … No examples of topological knotting were found in this case-by-case search” [8], and that “structures of globular proteins are ‘topologically simple’ and free of topologically complicated constructs such as knots and links and other types of entanglements” [9]. In none of these investigations, however, had any consideration been given to the possibility that catenation or knotting of the polypeptide chain might be effected through crosslinking by a combination of disulfide bonds and covalently bound cofactors.