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Tetanus toxin: Difference between revisions

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<table width='400' align='right' cellpadding='5'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'><StructureSection load='1fv2' size='400' side='right' caption='' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''Structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue''' (PDB entry [http://www.rcsb.org/pdb/explore/explore.do?structureId=1FV2 1fv2])  
<StructureSection load='1fv2' size='350' side='right' caption='Glycosylated C-terminal domain of tetanus toxin heavy chain complex with phosphate (PDB code [[1fv2]])' >
 
'''Structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue and phosphate''' (PDB entry [http://www.rcsb.org/pdb/explore/explore.do?structureId=1FV2 1fv2])  


<scene name='Sandbox_Reserved_403/Start_scene/1'>Initial Scene(minus phosphate ion)</scene>
<scene name='Sandbox_Reserved_403/Start_scene/1'>Initial Scene(minus phosphate ion)</scene>
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<scene name='Sandbox_Reserved_403/Sia7-sia6-binding_site/6'>/Remove GT1-b Analogue</scene>
<scene name='Sandbox_Reserved_403/Sia7-sia6-binding_site/6'>/Remove GT1-b Analogue</scene>


<scene name='Sandbox_Reserved_403/Binding_site_2/5'>Binding Site Residues Only</scene></center></td></tr></table>
<scene name='Sandbox_Reserved_403/Binding_site_2/5'>Binding Site Residues Only</scene>




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== ''Clostidium tetani'' ==
== ''Clostidium tetani'' ==


The Gram positive bacilli ''Clostridium tetani'' is the bacteria responsible for the disease state of tetanus.  The presence of the bacteria does not cause the disease but instead the toxins it produces cause the disease state. ''C. tetani'' produces two toxins; tetanospasmin and tetanolysin.  Tetanolysin is a cytolysin that increases the permeability of cellular membranes through cell lysis.<ref> PMID: 2404569</ref>  Tetanospasmin is the cause of tetanus and is sometimes referred to as tetanus neurotoxin (TeNT), as it acts on the central nervous system.  Tetanospasmin makes its way to the central nervous system via retrograde axonal flow beginning with α- motor neurons found in muscle and ending by binding to gangliosides found in the central nervous system (CNS).<ref> Bizzini B. Tetanus Toxin. Microbiological Reviews.1979 June;43(2):224-236.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC281472/pdf/microrev00006-0112.pdf?tool=pmcentrez]</ref>
The Gram positive bacilli ''Clostridium tetani'' is the bacteria responsible for the disease state of tetanus.  The presence of the bacteria does not cause the disease but instead the toxins it produces cause the disease state. ''C. tetani'' produces two toxins; '''tetanospasmin''' and '''tetanolysin''' or '''tentoxylysin'''.  Tetanolysin is a cytolysin that increases the permeability of cellular membranes through cell lysis.<ref> PMID: 2404569</ref>  Tetanospasmin is the cause of tetanus and is sometimes referred to as tetanus neurotoxin (TeNT), as it acts on the central nervous system.  Tetanospasmin makes its way to the central nervous system via retrograde axonal flow beginning with α- motor neurons found in muscle and ending by binding to gangliosides found in the central nervous system, i.e. CNS..<ref> Bizzini B. Tetanus Toxin. Microbiological Reviews.1979 June;43(2):224-236.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC281472/pdf/microrev00006-0112.pdf?tool=pmcentrez]</ref>


[[Image:Mechanism_of_action_of_tetanospasmin.jpg|thumb|350px|left|Mechanism of Action for Tetanospasmin.<ref> Mechanism of Action of Tetanospasmin (Dr. Arnab K Rana) [image on the internet]. 2005[updated 2005 Dec 26; cited 2011 Apr 20]. Available from: http://en.wikipedia.org/wiki/File:Mechanism_of_action_of_tetanospasmin.gif</ref>]]
[[Image:Mechanism_of_action_of_tetanospasmin.jpg|thumb|350px|left|Mechanism of Action for Tetanospasmin.<ref> Mechanism of Action of Tetanospasmin (Dr. Arnab K Rana) [image on the internet]. 2005[updated 2005 Dec 26; cited 2011 Apr 20]. Available from: http://en.wikipedia.org/wiki/File:Mechanism_of_action_of_tetanospasmin.gif</ref>]]
{{Clear}}
== Retrograde Axonal Transport ==
== Retrograde Axonal Transport ==


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[[Image:TeNT.jpg|thumb|200px|left|An overlap of three copies of the TeNT Hc structure.  This image helps to illustrate the two separte and distinct domains of the Hc fragment of tetanospasmin.<ref name="hcfrag" />]]
[[Image:TeNT.jpg|thumb|200px|left|An overlap of three copies of the TeNT Hc structure.  This image helps to illustrate the two separte and distinct domains of the Hc fragment of tetanospasmin.<ref name="hcfrag" />]]
 
{{Clear}}
Hc has two distinct domains:<ref name="hcfrag"> PMID:11418600</ref>
Hc has two distinct domains:<ref name="hcfrag"> PMID:11418600</ref>
[[Image:GT1-b ganglioside.jpg|thumb|350px|right|Ganglioside GT1-b.<ref name="hcfrag" />]]
[[Image:GT1-b ganglioside.jpg|thumb|350px|right|Ganglioside GT1-b.<ref name="hcfrag" />]]
 
{{Clear}}
   
   
1. Jelly-roll (amino end)
1. Jelly-roll (amino end)
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[[Image:GT1-b Ana.jpg|thumb|350px|right|GT1-b analogue which was used to bind to the Hc fragment in this study. The analogue differs from the native GT1-b in that Sia6 is the β-anomer and the ceramide group has been replaced.<ref name="hcfrag" />]]   
[[Image:GT1-b Ana.jpg|thumb|350px|right|GT1-b analogue which was used to bind to the Hc fragment in this study. The analogue differs from the native GT1-b in that Sia6 is the β-anomer and the ceramide group has been replaced.<ref name="hcfrag" />]]   
 
{{Clear}}
The Hc fragment has two binding sites in the β-trefoil domain:<ref name="hcfrag" />
The Hc fragment has two binding sites in the β-trefoil domain:<ref name="hcfrag" />


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</StructureSection>
==3D structures of tetanus toxin==
==3D structures of tetanus toxin==


===Tetanus toxin light chain===
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
 
{{#tree:id=OrganizedByTopic|openlevels=0|
[[1yvg]] - CtTeNT Lc – ''Clostridium tetani''<br />
[[1z7h]] - CtTeNT Lc (mutant)


===Tetanus toxin heavy chain===
*Tetanus toxin light chain


[[1dfq]], [[1yyn]] – CtTeNT Hc C terminal + sialic acid <br />
**[[1yvg]] - CtTeNT Lc 1-427 – ''Clostridium tetani''<br />
[[1diw]] - CtTeNT Hc C terminal + galactose<br />
**[[1z7h]], [[4j1l]], [[7by5]] - CtTeNT Lc (mutant)
[[1dil]] - CtTeNT Hc C terminal + lactose<br />
**[[7ce2]], [[7oh0]], [[7oh1]] - CtTeNT Lc 11-451 + antibody<br />
[[1d0h]] - CtTeNT Hc C terminal (mutant) + N-acetyl-galactosamine<br />
[[1fv2]], [[1fv3]] - CtTeNT Hc C terminal + ganglioside analog<br />
[[1yxw]] - CtTeNT Hc C terminal + tripeptide<br />
[[3hmy]] - CtTeNT Hc C terminal + GT2<br />
[[1hn1]] - CtTeNT Hc C terminal + GT2 + lactose


*Tetanus toxin heavy chain; Domains – translocation 459-865; receptor binding (RBD) 865-1315


**[[5n0b]], [[5n0c]] - CtTeNT (mutant)<br />
**[[1a8d]], [[1af9]] - CtTeNT Hc RBD (mutant)<br />
**[[1dfq]], [[1yyn]] – CtTeNT Hc + sialic acid <br />
**[[1diw]] - CtTeNT Hc + galactose<br />
**[[1dll]] - CtTeNT Hc + lactose<br />
**[[1d0h]] - CtTeNT Hc (mutant) + N-acetyl-galactosamine<br />
**[[1fv2]], [[1fv3]] - CtTeNT Hc RBD + ganglioside analog<br />
**[[1yxw]] - CtTeNT Hc RBD + tripeptide<br />
**[[3hmy]] - CtTeNT Hc RBD + GT2<br />
**[[3hn1]] - CtTeNT Hc RBD + GT2 + lactose
**[[7bxx]] - CtTeNT translocation domain (mutant)<br />
**[[7by4]] - CtTeNT RBD <br />


}}
==References==  
==References==  


<references />
<references />
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Jonathan G. Casto, Michal Harel, Alexander Berchansky
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