Linking in domain-swapped protein dimers

TL;DR

This study introduces a topology-based measure called Gaussian entanglement to analyze domain-swapped protein dimers, revealing significant intertwining patterns and correlations with biological properties, thus offering new insights into protein complex topology.

Contribution

The paper proposes a novel Gaussian entanglement parameter to quantify mutual entanglement in protein dimers, advancing the topological analysis of protein complexes.

Findings

High fraction of dimers with significant intertwining (|G'| > 1)

Nature favors negative mutual entanglement in dimers

Long dimers tend to have less intertwining

Abstract

The presence of knots has been observed in a small fraction of single-domain proteins and related to their thermodynamic and kinetic properties. The exchanging of identical structural elements, typical of domain-swapped proteins, make such dimers suitable candidates to validate the possibility that mutual entanglement between chains may play a similar role for protein complexes. We suggest that such entanglement is captured by the linking number. This represents, for two closed curves, the number of times that each curve winds around the other. We show that closing the curves is not necessary, as a novel parameter $G'$, termed Gaussian entanglement, is strongly correlated with the linking number. Based on $110$ non redundant domain-swapped dimers, our analysis evidences a high fraction of chains with a significant intertwining, that is with $|G'| > 1$. We report that Nature promotes configurations with negative mutual entanglement and surprisingly, it seems to suppress intertwining in long protein dimers. Supported by numerical simulations of dimer dissociation, our results provide a novel topology-based classification of protein-swapped dimers together with some preliminary evidence of its impact on their physical and biological properties.