Letters to Nature

Nature 406, 916-919 (24 August 2000) | doi:10.1038/35022623; Received 3 April 2000; Accepted 15 June 2000

A deeply knotted protein structure and how it might fold

William R. Taylor

  1. Division of Mathematical Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

Correspondence to: William R. Taylor Correspondence and requests for materials should be addressed to W.R.T. (e-mail: Email: wtaylor@nimr.mrc.ac.uk). The program used in this work can be found at ftp://mathbio.nimr.mrc.ac.uk.

The search for knots in protein has uncovered little that would cause Alexander the Great to reach for his sword. Excluding knots formed by post-translational crosslinking, the few proteins considered to be knotted form simple trefoil knots with one end of the chain extending through a loop by only a few residues1, 2, ten in the 'best' example3. A knot in an open chain (as distinct from a closed circle) is not rigorously defined and many weak protein knots disappear if the structure is viewed from a different angle. Here I describe a computer algorithm to detect knots in open chains that is not sensitive to viewpoint and that can define the region of the chain giving rise to the knot. It characterizes knots in proteins by the number of residues that must be removed from each end to abolish the knot. I applied this algorithm to the protein structure database and discovered a deep, figure-of-eight knot in the plant protein acetohydroxy acid isomeroreductase4. I propose a protein folding pathway that may explain how such a knot is formed.