7oh0: Difference between revisions
New page: '''Unreleased structure''' The entry 7oh0 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Tetanus neurotoxin HC domain in complex with TT104-Fab1== | |||
<StructureSection load='7oh0' size='340' side='right'caption='[[7oh0]], [[Resolution|resolution]] 3.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7oh0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_tetani Clostridium tetani] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OH0 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9Å</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=7oh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oh0 OCA], [https://pdbe.org/7oh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oh0 RCSB], [https://www.ebi.ac.uk/pdbsum/7oh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oh0 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We used human monoclonal antibodies (humAbs) to study the mechanism of neuron intoxication by tetanus neurotoxin and to evaluate these antibodies as a safe preventive and therapeutic substitute for hyperimmune sera to treat tetanus in mice. By screening memory B cells from immune donors, we selected 2 tetanus neurotoxin-specific mAbs with exceptionally high neutralizing activities and extensively characterized them both structurally and functionally. We found that these antibodies interfered with the binding and translocation of the neurotoxin into neurons by interacting with 2 epitopes, whose identification pinpoints crucial events in the cellular pathogenesis of tetanus. Our observations explain the neutralization ability of these antibodies, which we found to be exceptionally potent in preventing experimental tetanus when injected into mice long before the toxin. Moreover, their Fab derivatives neutralized tetanus neurotoxin in post-exposure experiments, suggesting their potential for therapeutic use via intrathecal injection. As such, we believe these humAbs, as well as their Fab derivatives, meet the requirements to be considered for prophylactic and therapeutic use in human tetanus and are ready for clinical trials. | |||
Exceptionally potent human monoclonal antibodies are effective for prophylaxis and treatment of tetanus in mice.,Pirazzini M, Grinzato A, Corti D, Barbieri S, Leka O, Vallese F, Tonellato M, Silacci-Fregni C, Piccoli L, Kandiah E, Schiavo G, Zanotti G, Lanzavecchia A, Montecucco C J Clin Invest. 2021 Nov 15;131(22):e151676. doi: 10.1172/JCI151676. PMID:34618682<ref>PMID:34618682</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7oh0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
*[[Tetanus toxin|Tetanus toxin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clostridium tetani]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Grinzato A]] | |||
[[Category: Kandiah E]] | |||
[[Category: Zanotti G]] | |||
Latest revision as of 16:50, 6 November 2024
Tetanus neurotoxin HC domain in complex with TT104-Fab1Tetanus neurotoxin HC domain in complex with TT104-Fab1
Structural highlights
FunctionTETX_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. Publication Abstract from PubMedWe used human monoclonal antibodies (humAbs) to study the mechanism of neuron intoxication by tetanus neurotoxin and to evaluate these antibodies as a safe preventive and therapeutic substitute for hyperimmune sera to treat tetanus in mice. By screening memory B cells from immune donors, we selected 2 tetanus neurotoxin-specific mAbs with exceptionally high neutralizing activities and extensively characterized them both structurally and functionally. We found that these antibodies interfered with the binding and translocation of the neurotoxin into neurons by interacting with 2 epitopes, whose identification pinpoints crucial events in the cellular pathogenesis of tetanus. Our observations explain the neutralization ability of these antibodies, which we found to be exceptionally potent in preventing experimental tetanus when injected into mice long before the toxin. Moreover, their Fab derivatives neutralized tetanus neurotoxin in post-exposure experiments, suggesting their potential for therapeutic use via intrathecal injection. As such, we believe these humAbs, as well as their Fab derivatives, meet the requirements to be considered for prophylactic and therapeutic use in human tetanus and are ready for clinical trials. Exceptionally potent human monoclonal antibodies are effective for prophylaxis and treatment of tetanus in mice.,Pirazzini M, Grinzato A, Corti D, Barbieri S, Leka O, Vallese F, Tonellato M, Silacci-Fregni C, Piccoli L, Kandiah E, Schiavo G, Zanotti G, Lanzavecchia A, Montecucco C J Clin Invest. 2021 Nov 15;131(22):e151676. doi: 10.1172/JCI151676. PMID:34618682[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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