In Search of Functional Advantages of Knots in Proteins

PLoS One. 2016 Nov 2;11(11):e0165986. doi: 10.1371/journal.pone.0165986. eCollection 2016.


We analysed the structure of deeply knotted proteins representing three unrelated families of knotted proteins. We looked at the correlation between positions of knotted cores in these proteins and such local structural characteristics as the number of intra-chain contacts, structural stability and solvent accessibility. We observed that the knotted cores and especially their borders showed strong enrichment in the number of contacts. These regions showed also increased thermal stability, whereas their solvent accessibility was decreased. Interestingly, the active sites within these knotted proteins preferentially located in the regions with increased number of contacts that also have increased thermal stability and decreased solvent accessibility. Our results suggest that knotting of polypeptide chains provides a favourable environment for the active sites observed in knotted proteins. Some knotted proteins have homologues without a knot. Interestingly, these unknotted homologues form local entanglements that retain structural characteristics of the knotted cores.

MeSH terms

  • Catalytic Domain
  • Models, Molecular
  • Protein Folding
  • Protein Stability
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Solvents / chemistry


  • Proteins
  • Solvents

Grants and funding

This work was supported by National Science Centre Poland #2012/07/E/NZ1/01900 (JIS) ; EMBO Installation Grant #2057 (JIS) ; Swiss National Science Foundation 31003A_166684 (AS) ; and the Leverhulme Trust RP2013-K-017 (AS) ; University of Warsaw, Faculty of Chemistry 120000-501/86-DSM-112 700 (PD-T) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.