Investigating the interaction of Grammostola rosea venom peptides and model lipid bilayers with solid-state NMR and electron microscopy techniques

Geraldine Polido, Xiangyan Shi, Dian Xu, Chengchen Guo, Rich Thai, Joseph P. Patterson, Nathan Gianneschi, Thomas M. Suchyna, Frederick Sachs, Gregory P. Holland*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Spider venom contains a number of small peptides that can control the gating properties of a wide range of ion channels with high affinity and specificity. These ion channels are responsible for coordination and control of many bodily functions such as transducing signals into sensory functions, smooth muscle contractions as well as serving as sensors in volume regulation. Hence, these peptides have been the topic of many research efforts in hopes that they can be used as biomedical therapeutics. Several peptides are known to control the gating properties of ion channels by involving the lipid membrane. GsMTx4, originally isolated from the Chilean Rose tarantula (Grammostola rosea), is known to selectively inhibit mechanosensitive ion channels by partitioning into the lipid bilayer. To further understand this indirect gating mechanism, we investigated the interactions between native GsAF2, VsTx1 and a synthetic form of GsMTx4 with model DMPC lipid bilayers using 31P solid-state NMR, 13C CP-MAS NMR, NS-TEM and cryo-TEM. The results reveal that these inhibitor cystine knot peptides perforate the DMPC lipid vesicles similarly with some subtle differences and ultimately create small spherical vesicles and anisotropic cylindrical and discoidal vesicles at concentrations near 1.0–1.5 mol% peptide. The anisotropic components align with their long axes along the NMR static B0 magnetic field, a property that should be useful in future NMR structural investigations of these systems. These findings move us forward in our understanding of how these peptides bind and interact with the lipid bilayer.

Original languageEnglish (US)
Pages (from-to)151-160
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • Electron microscopy
  • Inhibitor cystine knot (ICK)
  • Lipid bilayers
  • Solid-state NMR
  • Spider venom

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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