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Proposed Article Title: Knots in Proteins

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A piece of string, or a protein chain, is deemed to contain a knot when pulling on the ends would leave a knot. When the ends of most folded protein chains are "pulled", they resolve to a straight chain between the pulled ends: no knot remains. Knots in protein chains are rare, and the mechanisms by which they form and their functions remain subjects of speculation[1][2]. A dramatic example, discovered in 2000[1], is illustrated here.

Because knotted proteins are so rare, efforts have been made to disfavor knotted models when attempting to predict a protein fold[3].

physical pulling of ends? "the presence of the knot does not automatically indicate a superstable protein"[4]

"an unusually formed deep trefoil knot that stabilizes this region"[5]

"As expected, simulations of proteins with similar structure but with knot removed fold much more efficiently, clearly demonstrating the origin of these topological barriers."[6]

noncovalent pseudoknots [7]

??[8]

Notes & References

  1. 1.0 1.1 Taylor WR. A deeply knotted protein structure and how it might fold. Nature. 2000 Aug 24;406(6798):916-9. PMID:10972297 doi:10.1038/35022623
  2. Taylor WR. Protein knots and fold complexity: some new twists. Comput Biol Chem. 2007 Jun;31(3):151-62. Epub 2007 Mar 24. PMID:17500039 doi:10.1016/j.compbiolchem.2007.03.002
  3. Khatib F, Rohl CA, Karplus K. Pokefind: a novel topological filter for use with protein structure prediction. Bioinformatics. 2009 Jun 15;25(12):i281-8. PMID:19478000 doi:10.1093/bioinformatics/btp198
  4. Bornschlogl T, Anstrom DM, Mey E, Dzubiella J, Rief M, Forest KT. Tightening the knot in phytochrome by single-molecule atomic force microscopy. Biophys J. 2009 Feb 18;96(4):1508-14. PMID:19217867 doi:10.1016/j.bpj.2008.11.012
  5. Wagner JR, Brunzelle JS, Forest KT, Vierstra RD. A light-sensing knot revealed by the structure of the chromophore-binding domain of phytochrome. Nature. 2005 Nov 17;438(7066):325-31. PMID:16292304 doi:http://dx.doi.org/10.1038/nature04118
  6. PMCID: PMC2651233
  7. Taylor WR, Xiao B, Gamblin SJ, Lin K. A knot or not a knot? SETting the record 'straight' on proteins. Comput Biol Chem. 2003 Feb;27(1):11-5. PMID:12798035
  8. Andersson FI, Pina DG, Mallam AL, Blaser G, Jackson SE. Untangling the folding mechanism of the 5(2)-knotted protein UCH-L3. FEBS J. 2009 May;276(9):2625-35. Epub 2009 Mar 24. PMID:19476499 doi:10.1111/j.1742-4658.2009.06990.x

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Eric Martz, Eran Hodis

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