The What, Where, How and Why of Topological Knots in Proteins

Abstract: For decades it was thought that topological knots would never be formed by the polypeptide chain of any protein, knotting being incompatible with folding mechanisms. However, we now know that many proteins fold and form three-dimensional structures in which the chain crosses itself and threads through loop(s) to form knots. Proteins with very deep knots, i.e., a large part of the chain has passed through a knotting loop to form the knot have been identified, and four different classes of knots have been found embedded in protein strucutres: 3-1, 4-1, 5-2, and 6-1 knots. In addition, recently it has been established that a single polypeptide chain can contain more than one knot - several examples of tandem trefoil knotted proteins have been characterised. With the advent of the machine-learning based protein structure algorithm AlphaFold, several new classes of knotted protein have been predicted although their knotted structures have not yet been verified experimentally. Over twenty years, numerous experimental and computational studies on knotted proteins have investigated how such structures might form, in addition, to the properties of the knotted structure and whether they differ significantly or not from unknotted proteins. In this talk, I will review the field and explain 1) what knots are found in proteins and where they are within the folded structures, 2) the mechanisms by which knotted may fold, i., how the knots get there, and 3) why proteins may have evolved to form knotted structures. The talk will provide background on twenty years of research as well as discussing some state-of-the-art studies on designing proteins with novel knotted folds, as well as watching knotted proteins unfold and translocate through narrow pores.

geometric topology

Audience: researchers in the topic

( video )

GEOTOP-A seminar

Series comments: Web-seminar series on Applications of Geometry and Topology