View source for 3hmy


==Crystal structure of HCR/T complexed with GT2==
<StructureSection load='3hmy' size='340' side='right'caption='[[3hmy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3hmy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_tetani Clostridium tetani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HMY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmy OCA], [https://pdbe.org/3hmy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hmy RCSB], [https://www.ebi.ac.uk/pdbsum/3hmy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TETX_CLOTE TETX_CLOTE] Tetanus toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the '76-Gln-|-Phe-77' bond of synaptobrevin-2.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hm/3hmy_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hmy ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Tetanus neurotoxin (TeNT) is an exotoxin produced by Clostridium tetani that causes paralytic death to hundreds of thousands of humans annually. TeNT cleaves vesicle-associated membrane protein-2, which inhibits neurotransmitter release in the central nervous system to elicit spastic paralysis, but the molecular basis for TeNT entry into neurons remains unclear. TeNT is a approximately 150-kDa protein that has AB structure-function properties; the A domain is a zinc metalloprotease, and the B domain encodes a translocation domain and C-terminal receptor-binding domain (HCR/T). Earlier studies showed that HCR/T bound gangliosides via two carbohydrate-binding sites, termed the lactose-binding site (the "W" pocket) and the sialic acid-binding site (the "R" pocket). Here we report that TeNT high affinity binding to neurons is mediated solely by gangliosides. Glycan array and solid phase binding analyses identified gangliosides that bound exclusively to either the W pocket or the R pocket of TeNT; GM1a bound to the W pocket, and GD3 bound to the R pocket. Using these gangliosides and mutated forms of HCR/T that lacked one or both carbohydrate-binding pocket, gangliosides binding to both of the W and R pockets were shown to be necessary for high affinity binding to neuronal and non-neuronal cells. The crystal structure of a ternary complex of HCR/T with sugar components of two gangliosides bound to the W and R supported the binding of gangliosides to both carbohydrate pockets. These data show that gangliosides are functional dual receptors for TeNT.

Gangliosides as high affinity receptors for tetanus neurotoxin.,Chen C, Fu Z, Kim JJ, Barbieri JT, Baldwin MR J Biol Chem. 2009 Sep 25;284(39):26569-77. Epub 2009 Jul 14. PMID:19602728<ref>PMID:19602728</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3hmy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tetanus toxin|Tetanus toxin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium tetani]]
[[Category: Large Structures]]
[[Category: Baldwin MR]]
[[Category: Barbieri JT]]
[[Category: Chen C]]
[[Category: Fu Z]]
[[Category: Kim J-JP]]