User:Eric Martz/Sandbox 0

From Proteopedia

Jump to: navigation, search

Proposed Article Title: Knots in Proteins

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. In this article, only knots in the peptide-bonded amino acid chain are considered; knots resulting from disulfide bonds or hydrogen bonds are excluded. Knots in protein chains are rare, and the mechanisms by which they form and their functions remain subjects of experimentation and discussion[1][2][3][4]. Four types of knots have been found in protein chains, examples of three of which (41, 52, 61) are discussed below.


Knots Occurring in Proteins
Image:Overhand knot.jpg Image:Figure-of-eight-knot.jpg
Trefoil (overhand, 31) knot. Figure-of-eight (41) knot.
 
Image:Three-twist knot.jpg Image:Stevedores knot.jpg
Three-twist (52) knot. Stevedore's (61) knot.

Contents

Figure-of-eight knot in acetohydroxy acid isomeroreductase

William R. Taylor developed an algorithm for detecting knots in protein backbones, which he reported in 2000[1]. He scanned 3,440 sequence-different published protein structures from the Protein Data Bank. Only eight genuine knots were found, most of which were simple trefoil knots (overhand knots) and had been previously described. However several knots were detected in proteins not previously recognized as knotted. One was in acetohydroxy acid isomeroreductase ("AAIR", 1yve, 1qmg) , and was particularly interesting because of how deeply it sits in the folded protein backbone (far away from the ends) and because it is a more complicated figure-of-eight knot.

Taylor states "Pulling the ends of a given piece of string will usually decide whether it is knotted or not. Because we hold the ends, the string and our body form a closed circle and there is no danger of untying the knot as it is pulled." "The ends of protein chains (being charged) tend to lie on the surface ...." "An alternative approach is to invert the problem: rather than extending the termini outwards, these can be left fixed and the rest of the protein made to shrink around them. This was done [mathematically] by contracting the protein as if it were a rubber band."[1]

Reductoisomerase 1yve containing a figure-of-eight knot.

  Export Animated Image
  • Acetohydroxy acid isomeroreductase () from spinach (1yve) is the protein containing Taylor's figure-of-eight knot. Here is shown only one chain (I) of the biological unit, which is a homodimer.
Amino Terminus               Carboxy Terminus
  • Most of the chain is here , except for the knot-containing segment 312-545.
  • is shown here.
  • The ends of the knot-containing segment are fixed, while the intervening backbone mathematically (see Animation Methods).

  • For comparision, here (1tph), which has a similar length (247 residues) to the knotted region of 1yve (sequence range 312-545, length 234).
  • Mathematical shrinking, while fixing the positions of the ends, .

Subsequent to Taylor's work, figure-of-eight knots were found in three other ketol acid reductoisomerases, as well as in several phytochromes, a transcriptional regulator, and a virus core protein (see list at the pKnot server). Also, more complex knots were found, described below.

Knot Servers

These protein knot servers offer rotatable 3D graphics showing simplified knots.

pKnot

  • Server: pKnot[5].
  • Generates a morph "movie" of shrinking (holding the ends fixed), which can be played in OpenAstexViewer, or downloaded as a multiple-model PDB file, e.g. for animation in Jmol.
  • Visualization: appears to be in OpenAstexViewer. In Safari (but not in Firefox) on OS X, moving away from the browser tab containing the viewer causes the view to disappear when you return, and any options you checked to be lost.
  • Lists all knots in the PDB categorized by knot type (click the small link Knot table near the upper left of the main page, in a black bar). List includes core sequence range, and depth (but the "depth" is a single value not defined on the server). "Length" in the list appears to be the length of the entire protein chain, not the length of the knotted portion.
  • Upload PDB file: YES, and you can specify a sequence range for analysis.

knots.mit.edu

  • Server: knots.mit.edu[6].
  • Visualization: Jmol showing the chain with the knotted region colored, and the simplified knot (no movie).
  • Lists knots (a shorter list than at the pKnot server). List includes core sequence range plus other numbers that are not labeled. "Length" in the list appears to be the length of the entire protein chain, not the length of the knotted portion.
  • Upload PDB file: YES.

Notes

Knots do not appear to be associated with specific protein sequences[7].

"Our investigation of knotted structures in the Protein Data Bank reveals the most complicated knot discovered to date."[8].

6-1 stevedore knot, 2010[9]. "one could cleave more than 20 amino acids from the C-terminus and around 65 residues from the N-terminus without destroying the knotted topology." Animate their folding trajectory?

ends on surface, why? [10]

Because knotted proteins are so rare, efforts have been made to disfavor knotted models when attempting to predict a protein fold[11][12].

physical pulling of ends? "the presence of the knot does not automatically indicate a superstable protein"[13]

"an unusually formed deep trefoil knot that stabilizes this region"[14] "The studies of thermally and mechanically induced unfolding processes suggest a larger intrinsic stability of the protein with the knot."[15]

"As expected, simulations of proteins with similar structure but with knot removed fold much more efficiently, clearly demonstrating the origin of these topological barriers."[16] folding [17]

  • noncovalent pseudoknots [18]
  • cyclotide cyclic cystine knots[20]

Knot Categories

There are 176 pages mentioning "knot" in September, 2010, and 41 Categories that have been assigned automatically and suffer from many alternative phrases for the same thing. You can display the current list of "knots" categories using a search limited to the Category namespace:

Searching for the singular "knot" also gave 41 Categories in Sept. 2010.

Entries not in a knot category

A few pages that mention "knot" are not assigned to a knot Category.

  • 1mxi Methyltransferase with a Cofactor Bound at a Site Formed by a Knot
  • 2c4b INHIBITOR CYSTINE KNOT
  • 1k3r Methyltransferase with a Knot

Methods

Please see Knots in Proteins: Methods.

Content Attribution

Animations and models used in this article for the figure-of-eight knot were developed in August, 2000 by User:Eric Martz at Knots in Proteins, where the animations utilized the now defunct MDL Chime plugin.

Data for the figure-of-eight and unknotted comparison morphs were kindly provided by William R. Taylor (Division of Mathematical Biology, National Institute for Medical Research, the Ridgeway, Mill Hill, London UK) in 2000.

Notes & References

  1. 1.0 1.1 1.2 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. Dzubiella J. Sequence-specific size, structure, and stability of tight protein knots. Biophys J. 2009 Feb;96(3):831-9. PMID:19186124 doi:10.1016/j.bpj.2008.10.019
  4. Mallam AL, Morris ER, Jackson SE. Exploring knotting mechanisms in protein folding. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18740-5. Epub 2008 Nov 17. PMID:19015517
  5. Lai YL, Yen SC, Yu SH, Hwang JK. pKNOT: the protein KNOT web server. Nucleic Acids Res. 2007 Jul;35(Web Server issue):W420-4. Epub 2007 May 25. PMID:17526524 doi:10.1093/nar/gkm304
  6. Kolesov G, Virnau P, Kardar M, Mirny LA. Protein knot server: detection of knots in protein structures. Nucleic Acids Res. 2007 Jul;35(Web Server issue):W425-8. Epub 2007 May 21. PMID:17517776 doi:10.1093/nar/gkm312
  7. Potestio R, Micheletti C, Orland H. Knotted vs. unknotted proteins: evidence of knot-promoting loops. PLoS Comput Biol. 2010 Jul 29;6(7):e1000864. PMID:20686683 doi:10.1371/journal.pcbi.1000864
  8. Virnau P, Mirny LA, Kardar M. Intricate knots in proteins: Function and evolution. PLoS Comput Biol. 2006 Sep 15;2(9):e122. Epub 2006 Jul 28. PMID:16978047 doi:10.1371/journal.pcbi.0020122
  9. Bolinger D, Sulkowska JI, Hsu HP, Mirny LA, Kardar M, Onuchic JN, Virnau P. A Stevedore's protein knot. PLoS Comput Biol. 2010 Apr 1;6(4):e1000731. PMID:20369018 doi:10.1371/journal.pcbi.1000731
  10. Hovmoller S, Zhou T. Why are both ends of the polypeptide chain on the outside of proteins? Proteins. 2004 May 1;55(2):219-22. PMID:15048814 doi:10.1002/prot.20011
  11. 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
  12. Khatib F, Weirauch MT, Rohl CA. Rapid knot detection and application to protein structure prediction. Bioinformatics. 2006 Jul 15;22(14):e252-9. PMID:16873480 doi:22/14/e252
  13. 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
  14. 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
  15. Sulkowska JI, Sulkowski P, Szymczak P, Cieplak M. Stabilizing effect of knots on proteins. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19714-9. Epub 2008 Dec 8. PMID:19064918
  16. Sulkowska JI, Sulkowski P, Onuchic J. Dodging the crisis of folding proteins with knots. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3119-24. Epub 2009 Feb 11. PMID:19211785
  17. Gloss LM. Tying the knot that binds. Structure. 2007 Jan;15(1):2-4. PMID:17223526 doi:10.1016/j.str.2006.12.001
  18. 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
  19. 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
  20. Rosengren KJ, Daly NL, Plan MR, Waine C, Craik DJ. Twists, knots, and rings in proteins. Structural definition of the cyclotide framework. J Biol Chem. 2003 Mar 7;278(10):8606-16. Epub 2002 Dec 12. PMID:12482868 doi:10.1074/jbc.M211147200

Proteopedia Page Contributors and Editors (what is this?)

Eric Martz, Eran Hodis

Personal tools