A Stevedore's protein knot.

Daniel Bölinger,José N Onuchic,Joanna I Sułkowska,Hsiao-Ping Hsu,Mehran Kardar,Peter Virnau,Leonid A Mirny,William Taylor

doi:10.1371/journal.pcbi.1000731

Abstract

Protein knots, mostly regarded as intriguing oddities, are gradually being recognized as significant structural motifs. Seven distinctly knotted folds have already been identified. It is by and large unclear how these exceptional structures actually fold, and only recently, experiments and simulations have begun to shed some light on this issue. In checking the new protein structures submitted to the Protein Data Bank, we encountered the most complex and the smallest knots to date: A recently uncovered α-haloacid dehalogenase structure contains a knot with six crossings, a so-called Stevedore knot, in a projection onto a plane. The smallest protein knot is present in an as yet unclassified protein fragment that consists of only 92 amino acids. The topological complexity of the Stevedore knot presents a puzzle as to how it could possibly fold. To unravel this enigma, we performed folding simulations with a structure-based coarse-grained model and uncovered a possible mechanism by which the knot forms in a single loop flip.

Highlights

In the last decade, our knowledge about structure and characteristics of proteins has considerably expanded
The multitude of protein structures archived in the Protein Data Bank can be grouped into several hundred patterns, but only a handful are folded into knots
A microbial enzyme that catalyzes the breakdown of pollutants is the most complex protein knot encountered so far

Summary

Introduction

Our knowledge about structure and characteristics of proteins has considerably expanded. Not withstanding our daily experiences with shoelaces and cables, knots are mathematically only properly defined in closed loops, and not on open strings. In proteins, this issue can be resolved by connecting the termini (which are usually located on the surface) by an external loop [3,4,7]. This issue can be resolved by connecting the termini (which are usually located on the surface) by an external loop [3,4,7] This approach corresponds to a more practical definition of knottedness in which we demand that a knot remains on a string and tightens when we pull on both ends. Most of the knots in protein structures, were initially undetected from their structures since finding them by visual inspection is fairly hard, requiring a computational approach

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