Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers

@article{Suchyna2004BilayerdependentIO,
  title={Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers},
  author={T. Suchyna and S. E. Tape and R. Koeppe and O. Andersen and F. Sachs and P. Gottlieb},
  journal={Nature},
  year={2004},
  volume={430},
  pages={235-240}
}
The peptide GsMTx4, isolated from the venom of the tarantula Grammostola spatulata, is a selective inhibitor of stretch-activated cation channels (SACs). The mechanism of inhibition remains unknown; but both GsMTx4 and its enantiomer, enGsMTx4, modify the gating of SACs, thus violating a trademark of the traditional lock-and-key model of ligand–protein interactions. Suspecting a bilayer-dependent mechanism, we examined the effect of GsMTx4 and enGsMTx4 on gramicidin A (gA) channel gating. Both… Expand
GsMTx4: Mechanism of Inhibiting Mechanosensitive Ion Channels.
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A model placing GsMTx4 at the membrane surface, where it is stabilized by the lysines, and occupying a small fraction of the surface area in unstressed membranes is suggested, supported by molecular dynamics simulations of the peptide-monolayer system under different area constraints. Expand
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The spider peptide GsMTx4 exhibits a biphasic response in which peptide concentration determines inhibition or potentiation of activity in prokaryotic MS channels, showing the effect of different concentrations of extracellular Gs MTx4 on MS channels of small conductance, MscS and MscK in the cytoplasmic membrane of wild-type E. coli spheroplasts using the patch-clamp technique. Expand
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The results provide common mechanisms of peptide actions on MS channels and may give clues to therapeutic suppression of cardiac arrhythmias caused by excitatory currents through MS channels under hyper-mechanical stress in the heart. Expand
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A protocol is developed that allows the spontaneous assembly of a polypeptide toxin into membranes in atomistic molecular dynamics simulations of tens of nanoseconds and is found that the bilayer is about 2 Å thinner upon the binding of a GsMTx4 monomer. Expand
The activation mode of the mechanosensitive ion channel, MscL, by lysophosphatidylcholine differs from tension‐induced gating
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  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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TLDR
The activation mode of the mechanosensitive ion channel, MscL, by lysophosphatidylcholine differs from tension‐induced gating, leading to the conclusion that the mode of action of LPC is different from that of applied tension. Expand
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