Cotranslational folding of deeply knotted proteins

TL;DR

This study demonstrates that cotranslational folding on a model ribosome can significantly increase the likelihood of forming deeply knotted proteins, specifically trefoil knots, by using a structure-based model without non-native contacts.

Contribution

It shows that cotranslational folding enhances knot formation in deeply knotted proteins using a simplified ribosome model, revealing the mechanics and optimal conditions for knotting.

Findings

Cotranslational folding increases knot formation probability.

Knotting depends on temperature with an optimal point.

Folding often establishes native contacts without knot formation.

Abstract

Proper folding of deeply knotted proteins has a very low success rate even in structure-based models which favor formation of the native contacts but have no topological bias. By employing a structure-based model, we demonstrate that cotranslational folding on a model ribosome may enhance the odds to form trefoil knots for protein YibK without any need to introduce any non-native contacts. The ribosome is represented by a repulsive wall that keeps elongating the protein. On-ribosome folding proceeds through a a slipknot conformation. We elucidate the mechanics and energetics of its formation. We show that the knotting probability in on-ribosome folding is a function of temperature and that there is an optimal temperature for the process. Our model often leads to the establishment of the native contacts without formation of the knot.