Berlin 2024 – scientific programme

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BP: Fachverband Biologische Physik

BP 21: Poster IIIb

BP 21.19: Poster

Wednesday, March 20, 2024, 11:00–14:30, Poster C

Stability of the Pore Structure of α-Latrotoxin and the Unusual Ion Transport Mechanism through a Synaptic Membrane — •Azadeh Alavizargar and Andreas Heuer — Institute of Physical Chemistry, University of Muenster, Corrensstr. 28/30, 48149 Muenster, Germany

Latrotoxins (LaTXs) are presynaptic pore-forming neurotoxins found in the venom of Latrodectus spiders, known as black widows. Through the binding of LaTXs to specific receptors on the surface of neuronal cells, neurotransmitters are released by the formation of Ca2+-conducting tetrameric pores inside the membrane. The cryo-electron microscopy pre-pore and the pore structure of the α-LaTX has been resolved by the group of Christos Gastogiannis. However, the structure of the membrane part has not been characterized so far. Thus, the mechanism of ion transport through the membrane is still unclear.

Therefore, in this work we study the pore structure of α-LaTX, starting from the AlphaFold prediction, via molecular dynamics (MD) simulations also using Metadynamics. It turns out that the N-terminal is composed of a stable coiled-coiled bundle and a complex membrane-protein part. Specifically, we study the ion transport of Na+ and Ca2+ ions across the membrane. Surprisingly, the coiled-coiled region is not involved in the ion transport and the ions are attracted and finally crossed only through its membrane part. These results provide crucial insights towards the understanding of the mechanism of the LaTX family of neurotoxins.

Keywords: Latrotoxin; MD simulations; cryo-EM; coiled-coiled; ion transport