Knotted protein

The rotating view of a smoothed chain of a knotted protein (PDB ID: 1xd3)

Knotted proteins are proteins whose backbones entangle themselves in a knot. One can imagine pulling a protein chain from both termini, as though pulling a string from both ends. When a knotted protein is “pulled” from both termini, it does not get disentangled. Knotted proteins are very rare, making up only about one percent of the proteins in the Protein Data Bank, and their folding mechanisms and function are not well understood. Although there are experimental and theoretical studies that hint to some answers, systematic answers to these questions have not yet been found.

Although number of computational methods have been developed to detect protein knots, there are still no completely automatic methods to detect protein knots without necessary manual intervention due to the missing residues or chain breaks in the X-ray structures or the nonstandard PDB formats.

Most of the knots discovered in proteins are deep trefoil (31) knots. Figure eight knots (41), three-twist knots (52), Stevedore knots (61) and Septoil knot (71)[1] have also been discovered. Recently, use of machine learning techniques for predicting protein structure, resulted in highly accurate prediction of 63 knot.[2] Furthermore, using same techniques, composite knots (namely 31#31) were found[3] and crystallised.[4]

Four knot types identified in proteins: the 31 knot (upper left), the 41 knot (upper right), the 52 knots (lower left) and the 61 knot (lower right). These images were produced by KnotPlot.[5] Note that the 31 knot has in fact two distinct forms: left-handed and right-handed. What is shown here is a right-handed 31 knot.
  1. ^ Hsu, Min-Feng; Sriramoju, Manoj Kumar; Lai, Chih-Hsuan; Chen, Yun-Ru; Huang, Jing-Siou; Ko, Tzu-Ping; Huang, Kai-Fa; Hsu, Shang-Te Danny (January 2024). "Structure, dynamics, and stability of the smallest and most complex 71 protein knot". Journal of Biological Chemistry. 300 (1): 105553. doi:10.1016/j.jbc.2023.105553. ISSN 0021-9258. PMC 10840475. PMID 38072060.
  2. ^ Perlinska, Agata P.; Niemyska, Wanda H.; Gren, Bartosz A.; Rubach, Pawel; Sulkowska, Joanna I. (2022-01-01). "New 63 knot and other knots in human proteome from AlphaFold predictions". pp. 2021.12.30.474018. bioRxiv 10.1101/2021.12.30.474018.
  3. ^ Lan, Nguyen, Mai; Paulina, Perlinska, Agata; Ida, Sulkowska, Joanna; Smita, Pilla; Emilia, Staszor; Iwona, Lewandowska; Rafal, Augustyniak (2024). "Are there double knots in proteins? Prediction and in vitro verification based on TrmD-Tm1570 fusion from C. nitroreducens". Frontiers in Molecular Biosciences. 10. doi:10.3389/fmolb.2023.1223830. ISSN 2296-889X. PMC 11187310.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Bruno da Silva, Fernando; Lewandowska, Iwona; Kluza, Anna; Niewieczerzal, Szymon; Augustyniak, Rafał; Sulkowska, Joanna I. (14 March 2023). ""First crystal structure of double knotted protein TrmD-Tm1570 – inside from degradation perspective"". bioRxiv. doi:10.1101/2023.03.13.532328. S2CID 257559424.
  5. ^ Robert, Scharein. "KnotPlot: Hypnagogic Software (Version 0.1)". Nearly all of the images here were created with KnotPlot, a fairly elaborate program to visualize and manipulate mathematical knots in three and four dimensions.