KnotProt: a database of proteins with knots and slipknots

Abstract

The protein topology database KnotProt, http://knotprot.cent.uw.edu.pl/, collects information about protein structures with open polypeptide chains forming knots or slipknots. The knotting complexity of the cataloged proteins is presented in the form of a matrix diagram that shows users the knot type of the entire polypeptide chain and of each of its subchains. The pattern visible in the matrix gives the knotting fingerprint of a given protein and permits users to determine, for example, the minimal length of the knotted regions (knot's core size) or the depth of a knot, i.e. how many amino acids can be removed from either end of the cataloged protein structure before converting it from a knot to a different type of knot. In addition, the database presents extensive information about the biological functions, families and fold types of proteins with non-trivial knotting. As an additional feature, the KnotProt database enables users to submit protein or polymer chains and generate their knotting fingerprints.

Figure 1.

An example of data presentation for a knotted protein (PDB code 1yrl) in the KnotProt database. In this example the analyzed polypeptide chain of Escherichia coli ketol-acid reductoisomerase reveals that the entire polypeptide chain forms a 4₁ knot, and has a subchain forming a 3₁ knot. Diagram in top left: knotting fingerprint revealing the positions of subchains forming 4₁ and 3₁ knots. Top right: graphical representation of protein structure in JSmol. Table in the middle: detailed data about knots and slipknots formed by backbone subchains. Bottom: sequence representation with the knot core and knot tails highlighted in appropriate colors.

Figure 2.

A protein with a trefoil (3₁) knot (middle panel). Left panel: schematic representation of trefoil (3₁) knot in an open chain. Right panel: simplified representation of the backbone chain of the protein in the middle panel, obtained after chain closure and simplification by the KMT algorithm (see the main text). The KnotProt uses such simplified polygonal configurations to calculate knot polynomials.

Figure 3.

Examples of knotting fingerprints (figure from (1)) for a knot (A) and two slipknots (B and C). For a knot (panel A) the shaded area necessarily includes a point in the left-bottom corner of the diagram. For slipknots (B and C) this point is not included in the shaded area.

Figure 4.

Missing atoms are denoted by gray strips in the knotting fingerprint, example based on protein 2cav. If a PDB structure contains missing atoms, its knotting type may depend on the space configuration of the missing segment and the knotting type of the chain may not be properly detected in the KnotProt—a user should be careful when interpreting such results.

Figure 5.

Searching the KnotProt database according to the knot or slipknot type. A schematic graphical representation is shown for each knot type, including its chirality. All structures in PDB that do not contain knots are listed under ‘Unknots.’ Structures for which a knot type is most likely improperly determined, e.g. due to missing atoms, are collected under ‘Artifacts.’

Figure 6.

The number of proteins with knots and slipknots (from the KnotProt) contained in the PDB by year.