Multiple folding pathways of proteins with shallow knots and co-translational folding

TL;DR

This study explores the complex folding pathways of shallowly knotted proteins, revealing multiple mechanisms, temperature effects, and the influence of co-translational conditions on successful folding.

Contribution

It uncovers new two-loop folding mechanisms and demonstrates the impact of temperature and nascent conditions on protein knotting.

Findings

Multiple folding pathways including novel two-loop mechanisms

Optimal folding occurs at higher temperatures than fastest folding

Co-translational folding favors knot formation

Abstract

We study the folding process in the shallowly knotted protein MJ0366 within two variants of a structure-based model. We observe that the resulting topological pathways are much richer than identified in previous studies. In addition to the single knot-loop events, we find novel, and dominant, two-loop mechanisms. We demonstrate that folding takes place in a range of temperatures and the conditions of most successful folding are at temperatures which are higher than those required for the fastest folding. We also demonstrate that nascent conditions are more favorable to knotting than off-ribosome folding.