Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions.

ABSTRACT: Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of the Ca_V2.3 subtype. Two mechanisms dominate the binding process of cysteine-rich peptides: 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 in the membrane, a preference for binding towards partially negatively charged membranes, and that

SUBMITTER: Mellado G 

PROVIDER: S-EPMC9231009 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature