Formation of Cystine Slipknots in Dimeric Proteins

TL;DR

This paper investigates the mechanical stability of cystine knot proteins, revealing that dimeric forms exhibit high resistance to stretching due to cystine slipknots, with stability depending on pulling direction and dimer configuration.

Contribution

It demonstrates that cystine knot proteins, especially dimers, have significant mechanostability due to slipknots, and explores how pulling direction affects this stability.

Findings

Dimeric cystine knot proteins are more resistant to stretching than titin.

Formation of cystine slipknots underlies high mechanostability.

Mechanostability varies with pulling direction and dimer configuration.

Abstract

We consider mechanical stability of dimeric and monomeric proteins with the cystine knot motif. A structure based dynamical model is used to demonstrate that all dimeric and some monomeric proteins of this kind should have considerable resistance to stretching that is significantly larger than that of titin. The mechanisms of the large mechanostability are elucidated. In most cases, it originates from the induced formation of one or two cystine slipknots. Since there are four termini in a dimer, there are several ways of selecting two of them to pull by. We show that in the cystine knot systems, there is strong anisotropy in mechanostability and force patterns related to the selection. We show that the thermodynamic stability of the dimers is enhanced compared to the constituting monomers whereas machanostability is either lower or higher.