How knots influence properties of proteins

TL;DR

This study uses molecular dynamics to investigate how the presence of a knot affects the stability and unfolding behavior of proteins within the transcarbamylase family.

Contribution

It provides new insights into the impact of protein knots on stability by comparing proteins with and without knots using coarse-grained models.

Findings

Knotted proteins show increased intrinsic stability.

Knot presence influences unfolding pathways.

Knot removal decreases stability.

Abstract

Molecular dynamics studies within a coarse-grained structure based model were used on two similar proteins belonging to the transcarbamylase family to probe the effects in the native structure of a knot. The first protein, N-acetylornithine transcarbamylase, contains no knot whereas human ormithine transcarbamylase contains a trefoil knot located deep within the sequence. In addition, we also analyzed a modified transferase with the knot removed by the appropriate change of a knot-making crossing of the protein chain. The studies of thermally- and mechanically-induced unfolding processes suggest a larger intrinsic stability of the protein with the knot.