The Folding of Knotted Proteins: Distinguishing the Distinct Behavior of Shallow and Deep Knots

Abstract

Abstract The mechanism of deep knot formation in proteins has been debated for the past two decades, but definitive answers are still lacking. In this review, we first describe knotted proteins from the perspective of shallow and deep knots, taking into account recent experimental and theoretical results. We focus on the folding mechanism, where this difference is most profound. We explain in more details the cotranslational knotting pathway. Then, we additionally show that proteins with extremely deep knots have a distinct mechanism of knotting from proteins with shallow knots. The approach based on treating shallow and deep knots as separate classes of molecules allow to classify them better and introduce a new paradigm of thinking about knotted proteins as such. This may in turn help to avoid ambiguities in further research.