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Proposed Article Title: Knots in Proteins
Proposed Article Title: [[Knots in proteins|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<ref name="taylor2000">PMID: 10972297</ref><ref name="taylor2007">PMID: 17500039</ref><ref>PMID: 19186124</ref><ref>PMID: 19015517</ref>. Four types of knots have been found in protein chains, examples of three of which (4<sub>1</sub>, 5<sub>2</sub>, 6<sub>1</sub>) are discussed below.
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<ref name="taylor2000">PMID: 10972297</ref><ref name="taylor2007">PMID: 17500039</ref><ref>PMID: 19186124</ref><ref>PMID: 19015517</ref>. Four types of knots have been found in protein chains, examples of three of which (4<sub>1</sub>, 5<sub>2</sub>, 6<sub>1</sub>) are discussed below.


<table class="wikitable" align="right" width="260">
<table class="wikitable" align="right" width="260">
<tr>
<tr>
<td colspan="2"><center>Knots Occurring in Proteins</center></td>
</tr><tr>
<td>[[Image:Overhand knot.jpg]]</td>
<td>[[Image:Overhand knot.jpg]]</td>
<td>[[Image:Figure-of-eight-knot.jpg]]</td>
<td>[[Image:Figure-of-eight-knot.jpg]]</td>
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<td colspan="2">&nbsp;</td>
<td colspan="2">&nbsp;</td>
</tr><tr>
</tr><tr>
<td>[[Image:Overhand knot.jpg]]</td>
<td>[[Image:Three-twist knot.jpg]]</td>
<td>[[Image:Figure-of-eight-knot.jpg]]</td>
<td>[[Image:Stevedores knot.jpg]]</td>
</tr><tr>
</tr><tr>
<td>Three-twist [http://en.wikipedia.org/wiki/Crossing_number_(knot_theory) 5<sub>2</sub>]) knot.</td>
<td>Three-twist ([http://en.wikipedia.org/wiki/Crossing_number_(knot_theory) 5<sub>2</sub>]) knot.</td>
<td>Stevedore's ([http://en.wikipedia.org/wiki/Crossing_number_(knot_theory) 6<sub>1</sub>]) knot.</td>
<td>Stevedore's ([http://en.wikipedia.org/wiki/Crossing_number_(knot_theory) 6<sub>1</sub>]) knot.</td>
</tr></table>
</tr></table>


 
__TOC__
 
{{Clear}}
==Figure-of-eight knot in acetohydroxy acid isomeroreductase==
==Figure-of-eight knot in acetohydroxy acid isomeroreductase==


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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."<ref name="taylor2000" />
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."<ref name="taylor2000" />


<applet load='Insert PDB code or filename here' size='400' frame='true' align='right' caption='Insert caption here'
<applet load='Insert PDB code or filename here' size='400' frame='true' align='right' caption='Reductoisomerase [[1yve]] containing a figure-of-eight knot.'
scene='User:Eric_Martz/Sandbox_0/1yve_chain_i_rockets/2' />
scene='User:Eric_Martz/Sandbox_0/1yve_chain_i_rockets/2' />


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*<scene name='User:Eric_Martz/Sandbox_0/1yve_chain_i_knot_only/2'>Only the knot-containing segment 312-545</scene> is shown here.
*<scene name='User:Eric_Martz/Sandbox_0/1yve_chain_i_knot_only/2'>Only the knot-containing segment 312-545</scene> is shown here.


*The ends of the knot-containing segment are fixed, while the intervening backbone mathematically <scene name='User:Eric_Martz/Sandbox_0/Knot_pull_morph_1yve/2'>shrinks revealing the knot</scene>.
*The ends of the knot-containing segment are fixed, while the intervening backbone mathematically <scene name='User:Eric_Martz/Sandbox_0/Knot_pull_morph_1yve/2'>shrinks revealing the knot</scene> (see [[Knots in Proteins: Methods|Animation Methods]]).
{{Template:Button_Toggle_Animation2}}
{{Template:Button_Toggle_Animation2}}
*For comparision, here <scene name='User:Eric_Martz/Sandbox_0/1tph_rockets/1'>chain "1" of triosephosphate isomerase</scene> ([[1tph]]), which has a similar length (247 residues) to the knotted region of 1yve (sequence range 312-545, length 234).
*For comparision, here <scene name='User:Eric_Martz/Sandbox_0/1tph_rockets/1'>chain "1" of triosephosphate isomerase</scene> ([[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, <scene name='User:Eric_Martz/Sandbox_0/1tph_noknot_morph/3'>reveals that no knot is present</scene>.
*Mathematical shrinking, while fixing the positions of the ends, <scene name='User:Eric_Martz/Sandbox_0/1tph_noknot_morph/3'>reveals that no knot is present</scene>.
 
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 [http://pknot.life.nctu.edu.tw/table_new.php list at the pKnot server]). Also, more complex knots were found, described below.


==Knot Servers==
==Knot Servers==
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*Server: [http://pknot.life.nctu.edu.tw/ pKnot]<ref>PMID: 17526524</ref>.
*Server: [http://pknot.life.nctu.edu.tw/ pKnot]<ref>PMID: 17526524</ref>.
*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]].
*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 [http://www.openastexviewer.net/web/ OpenAstexViewer]. In Safari 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.
*Visualization: appears to be in [http://www.openastexviewer.net/web/ 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.
*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.
*Upload PDB file: YES, and you can specify a sequence range for analysis.
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==Methods==
==Methods==
Please see [[Knots in Proteins - Methods]].
Please see [[Knots in Proteins: Methods]].


==Content Attribution==
==Content Attribution==
Animations and models used in this article were developed in August, 2000 by [[User:Eric Martz]] at [http://www.umass.edu/microbio/chime/knots/ Knots in Proteins], where the animations utilized the now defunct [http://www.umass.edu/microbio/chime/abtchime.htm MDL Chime plugin].
Animations and models used in this article for the figure-of-eight knot were developed in August, 2000 by [[User:Eric Martz]] at [http://www.umass.edu/microbio/chime/knots/ Knots in Proteins], where the animations utilized the now defunct [http://www.umass.edu/microbio/chime/abtchime.htm MDL Chime plugin].


Data for the above morphs were kindly provided by William R. Taylor ([http://mathbio.nimr.mrc.ac.uk/ Division of Mathematical Biology, National Institute for Medical Research, the Ridgeway, Mill Hill, London UK]).
Data for the figure-of-eight and unknotted comparison morphs were kindly provided by William R. Taylor ([http://mathbio.nimr.mrc.ac.uk/ Division of Mathematical Biology, National Institute for Medical Research, the Ridgeway, Mill Hill, London UK]) in 2000.


==Notes & References==
==Notes & References==
<references />
<references />