View source for 9go9


==Prepore state of alpha-Latrotoxin==
<StructureSection load='9go9' size='340' side='right'caption='[[9go9]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9go9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Latrodectus_tredecimguttatus Latrodectus tredecimguttatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9GO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9GO9 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]] 2.7&#8491;</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=9go9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9go9 OCA], [https://pdbe.org/9go9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9go9 RCSB], [https://www.ebi.ac.uk/pdbsum/9go9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9go9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LATA_LATTR LATA_LATTR] Presynaptic neurotoxin that causes massive release of neurotransmitters from vertebrate (but not invertebrate) nerve terminals and endocrine cells via a complex mechanism involving activation of receptor(s) and toxin insertion into the plasma membrane with subsequent pore formation. Binds to neurexin-1-alpha (NRXN1) in a calcium dependent manner, adhesion G protein-coupled receptor L1 (ADGRL1, also termed latrophilin-1 and calcium-independent receptor of latrotoxin (CIRL)), and receptor-type tyrosine-protein phosphatase S (PTPRS), also termed PTP sigma (PubMed:12110683, PubMed:7592578, PubMed:8798521). NRXN1 and PTPRS are suggested to provide a platform for binding and subsequent pore formation events (PubMed:11572875, PubMed:9799228). In contrast, binding to ADGRL1 does not involve oligomerization and channel formation, but direct downstream stimulation of the synaptic fusion machinery (PubMed:12764091).<ref>PMID:11572875</ref> <ref>PMID:12110683</ref> <ref>PMID:12764091</ref> <ref>PMID:7592578</ref> <ref>PMID:8798521</ref> <ref>PMID:9799228</ref> 
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== Publication Abstract from PubMed ==
The potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, alpha-LTX, targets vertebrates. This 130 kDa toxin binds to receptors at presynaptic nerve terminals and triggers a massive release of neurotransmitters. It is widely accepted that LTXs tetramerize and insert into the presynaptic membrane, thereby forming Ca(2+)-conductive pores, but the underlying mechanism remains poorly understood. LTXs are homologous and consist of an N-terminal region with three distinct domains, along with a C-terminal domain containing up to 22 consecutive ankyrin repeats. Here we report cryoEM structures of the vertebrate-specific alpha-LTX tetramer in its prepore and pore state. Our structures, in combination with AlphaFold2-based structural modeling and molecular dynamics simulations, reveal dramatic conformational changes in the N-terminal region of the complex. Four distinct helical bundles rearrange and together form a highly stable, 15 nm long, cation-impermeable coiled-coil stalk. This stalk, in turn, positions an N-terminal pair of helices within the membrane, thereby enabling the assembly of a cation-permeable channel. Taken together, these data give insight into a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications.

Structural basis of alpha-latrotoxin transition to a cation-selective pore.,Klink BU, Alavizargar A, Kalyankumar KS, Chen M, Heuer A, Gatsogiannis C Nat Commun. 2024 Oct 3;15(1):8551. doi: 10.1038/s41467-024-52635-5. PMID:39362850<ref>PMID:39362850</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 9go9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Latrodectus tredecimguttatus]]
[[Category: Gatsogiannis C]]
[[Category: Kalyankumar KS]]
[[Category: Klink BU]]