Website Update: Email Subscriptions Discontinued

Posted by
  Website Update: Email Subscriptions Discontinued I want to share an important update regarding email subscriptions and newsletters on Arácnido Taxonomy. Effective immediately, I have discontinued using Mailchimp for email newsletter subscriptions. Over the past several days, the subscription system and associated website functions have been subjected to persistent automated bot activity and attempted exploitation. In addition to generating unwanted subscription activity, these requests have contributed to periods of reduced website performance. To help protect the website, its content, and legitimate visitors, the Mailchimp subscription and registration functions have been removed. Following Arácnido Taxonomy via RSS For the foreseeable future, RSS will be the primary way to subscribe to and follow new posts and updates from Arácnido Taxonomy. RSS provides a simple, direct way to receive new content without submitting an email address or creating an account. Once the Arácnido Ta...

Molecular mechanism of α-latrotoxin action

Posted by

 

Molecular mechanism of α-latrotoxin action

Abstract


The potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, α-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 Ca2+-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 the first high resolution structures of the vertebrate-specific α-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 synchronously rearrange to progressively form a highly stable 15 nm 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 unveil 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.


Molecular mechanism of α-latrotoxin action Bjoern Udo Klink, Azadeh Alavizargar, Kalyankumar Karthik Subramaniam, Minghao Chen, Andreas Heuer, Christos Gatsogiannis
bioRxiv 2024.03.06.583760; doi: https://doi.org/10.1101/2024.03.06.583760