The presence of physical knots has been observed in a small fraction of single-domain proteins and related to their thermodynamic and kinetic properties. The entanglement between different chains in multimeric protein complexes, as captured by their linking number, may as well represent a significant topological feature. The exchanging of identical structural elements  typical of domain-swapped proteins make them suitable candidates to validate this possibility . Here we analyze 110 non redundant domain-swapped dimers filtered from the 3Dswap and Proswap databases, by keeping only structures not affected by the presence of holes along the main backbone chain. The linking number G' determined by Gauss integrals on the C_\alpha backbones is shown to be a solid and efficient tool for quantifying the mutual entanglement, also due to its strong correlation with the topological linking averaged over many closures of the chains. Our analysis evidences a quite high fraction of chains with a significant linking , that is with |G'| > 1. We report that Nature promotes configurations with G'<0 and surprisingly, it seems to suppress linking of long proteins. While proteins composed of about 100 residues can be well linked in the swapped dimer form, this is not observed for much longer chains. Upon dissociationof a few dimers via numerical simulations, we observe an exponential decay of the linking number with time, providing an additional useful characterization of the entanglement within swapped dimers. Our results provide a novel and robust topology-based classification of protein-swapped dimers together with some preliminary evidence of its impact on their physical and biological properties.
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.
D
physical
D
entanglement between different chains in multimeric protein complexes, as captured by their linking number, may as well represent a significant topological feature. The
A
,
R
make them
, make such dimers
R
this possibility . Here we analyze
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
R
dimers filtered from the 3Dswap and Proswap databases, by keeping only structures not affected by the presence of holes along the main backbone chain. The linking number G' determined by Gauss integrals on the C_\alpha backbones is shown to be a solid and efficient tool for quantifying the mutual entanglement, also due to its strong correlation with the topological linking averaged over many closures of the chains. Our
dimers, our
D
quite
R
linking
intertwining
R
G'<0
negative mutual entanglement
R
linking of long proteins. While proteins composed of about 100 residues can be well linked in the swapped dimer form, this is not observed for much longer chains. Upon dissociationof a few dimers via numerical simulations, we observe an exponential decay of the linking number with time, providing an additional useful characterization of the entanglement within swapped dimers. Our
intertwining in long protein dimers. Supported by numerical simulations of dimer dissociation, our
D
and robust