A deeply knotted protein structure and how it might fold.

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Protein knotting is rare, with most known knots being simple trefoil types.
• Existing methods for identifying protein knots are often viewpoint-dependent and lack rigor for open chains.

Purpose of the Study:

• To develop a robust computational algorithm for detecting knots in open protein chains.
• To identify and characterize complex knots within the protein structure database.

Main Methods:

• Development of a viewpoint-independent computer algorithm to detect and characterize knots in open chains.
• Application of the algorithm to the protein structure database.
• Analysis of knot complexity based on the number of residues to remove from chain ends.

Main Results:

• Discovery of a deep, figure-of-eight knot in the plant protein acetohydroxy acid isomeroreductase.
• The algorithm successfully identified knots irrespective of viewing angle and quantified their complexity.
• Characterization of the knot region within the protein chain.

Conclusions:

• The developed algorithm provides a reliable method for identifying and characterizing protein knots.
• The discovery of a complex knot suggests novel protein folding pathways.
• Further investigation into the proposed folding pathway for acetohydroxy acid isomeroreductase is warranted.