View source for 9fyq


==Cryo-EM structure of native SV2A in complex with TeNT-Hc, gangliosides and Pro-Macrobody 5==
<StructureSection load='9fyq' size='340' side='right'caption='[[9fyq]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fyq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_tetani_E88 Clostridium tetani E88], [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FYQ 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]] 3.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6UZ:OMEGA-UNDECYLENYL-BETA-D-MALTOPYRANOSIDE'>6UZ</scene>, <scene name='pdbligand=A1IHM:(2~{R},4~{R},5~{S},6~{S})-2-[(2~{R},3~{R})-3-[(2~{R},3~{S},4~{S},6~{S})-6-[(2~{S},3~{S},4~{R},5~{S},6~{S})-3-[(2~{R},3~{R},4~{R},5~{S},6~{R})-3-acetamido-6-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-2-yl]oxy-2-(hydroxymethyl)-6-[(2~{R},3~{R},4~{R},5~{R},6~{S})-2-(hydroxymethyl)-6-[2-(octadecanoylamino)-3-oxidanyl-octadec-4-enoxy]-4,5-bis(oxidanyl)oxan-3-yl]oxy-5-oxidanyl-oxan-4-yl]oxy-3-azanyl-6-carboxy-4-oxidanyl-oxan-2-yl]-2,3-bis(oxidanyl)propoxy]-5-azanyl-4-oxidanyl-6-[(1~{R},2~{S})-1,2,3-tris(oxidanyl)propyl]oxane-2-carboxylic+acid'>A1IHM</scene>, <scene name='pdbligand=A1IHN:(2~{S},4~{S},5~{R},6~{S})-5-acetamido-2-[(2~{R},3~{R},4~{R},5~{S},6~{R})-2-[(2~{R},3~{R},4~{S},5~{R},6~{S})-2-[(2~{R},3~{S},4~{R},5~{R},6~{R})-4-[(2~{S},4~{S},5~{S},6~{S})-5-acetamido-2-carboxy-4-oxidanyl-6-[(1~{S},2~{R})-1,2,3-tris(oxidanyl)propyl]oxan-2-yl]oxy-6-[(2~{R},3~{S},4~{R},5~{R},6~{R})-6-[2-(docosanoylamino)-3-oxidanyl-octadec-4-enoxy]-2-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-3-yl]oxy-2-(hydroxymethyl)-5-oxidanyl-oxan-3-yl]oxy-6-(hydroxymethyl)-5-oxidanyl-3-(2-oxidanylidenepropyl)oxan-4-yl]oxy-6-(hydroxymethyl)-3,5-bis(oxidanyl)oxan-4-yl]oxy-4-oxidanyl-6-[(1~{R},2~{R})-1,2,3-tris(oxidanyl)propyl]oxane-2-carboxylic+acid'>A1IHN</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9fyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fyq OCA], [https://pdbe.org/9fyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fyq RCSB], [https://www.ebi.ac.uk/pdbsum/9fyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fyq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A836APF1_SHEEP A0A836APF1_SHEEP] Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles.[ARBA:ARBA00037074]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The synaptic vesicle glycoprotein 2A (SV2A) is a synaptic vesicle (SV) resident with homology to the major facilitator superfamily (MFS) and essential in vertebrate neurotransmission. Despite its unclear physiological role, SV2A is of high medical relevance as it is the target of the anti-epileptic drug Levetiracetam (LEV) and a receptor for clostridial neurotoxins (CNTs), among them presumably tetanus neurotoxin (TeNT). To obtain detailed insights about these molecular interactions we subjected native SV2A, purified from brain tissue, to cryo-EM. We discover that TeNT binds SV2A strikingly different from botulinum neurotoxin A and unveil the precise geometry of TeNT binding to dipartite SV2-ganglioside receptors. The structures deliver compelling support for SV2A as the protein receptor for TeNT in central neurons and reinforce the concepts of the dual receptor hypothesis for CNT entry into neurons. Further, our LEV-bound structure of SV2A reveals the drug-interacting residues, delineates a putative substrate pocket in SV2A and provides insights into the SV2-isoform-specificity of LEV. Our work has implications for CNT engineering from a hitherto unrecognized SV2 binding interface and for improved designs of anti-convulsant drugs in epilepsy treatment.

Structures of native SV2A reveal the binding mode for tetanus neurotoxin and anti-epileptic racetams.,Schenck S, Laeremans T, Steyaert J, Brunner JD Nat Commun. 2025 May 5;16(1):4172. doi: 10.1038/s41467-025-59545-0. PMID:40325068<ref>PMID:40325068</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9fyq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium tetani E88]]
[[Category: Escherichia coli K-12]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Ovis aries]]
[[Category: Brunner JD]]
[[Category: Schenck S]]