Version 1
: Received: 29 December 2021 / Approved: 31 December 2021 / Online: 31 December 2021 (09:35:18 CET)
How to cite:
Mellado, G.; Garate, J.A.; Neely, A. Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions. Preprints2021, 2021120496. https://doi.org/10.20944/preprints202112.0496.v1
Mellado, G.; Garate, J.A.; Neely, A. Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions. Preprints 2021, 2021120496. https://doi.org/10.20944/preprints202112.0496.v1
Mellado, G.; Garate, J.A.; Neely, A. Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions. Preprints2021, 2021120496. https://doi.org/10.20944/preprints202112.0496.v1
APA Style
Mellado, G., Garate, J.A., & Neely, A. (2021). Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions. Preprints. https://doi.org/10.20944/preprints202112.0496.v1
Chicago/Turabian Style
Mellado, G., Jose Antonio Garate and Alan Neely. 2021 "Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions" Preprints. https://doi.org/10.20944/preprints202112.0496.v1
Abstract
Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of CaV2.3 subtype. Two general binding mechanisms are present in nature: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts within the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics drives membrane binding. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determin-ing the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482
Chemistry and Materials Science, Physical Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.