Related Experiment Video

Updated: Oct 3, 2026

Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
11:44

Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities

Published on: October 2, 2018

Evolution of maurotoxin conformation and blocking efficacy towards Shaker B channels during the course of folding and

Eric di Luccio1, Alessandra Matavel, Sandrine Opi

  • 1CNRS UMR 6560, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France.

The Biochemical Journal
|January 5, 2002
PubMed

Insights

Maurotoxin folding reveals dynamic structural changes affecting its potassium channel blocking activity. Initially potent, synthetic maurotoxin

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Maurotoxin (MTX) is a scorpion-derived peptide toxin.
  • MTX targets various potassium (K+) channels, including the Shaker B subtype.
  • The toxin's structure is stabilized by four disulfide bridges.

Purpose of the Study:

  • To investigate the in vitro folding kinetics of synthetic MTX (sMTX).
  • To correlate disulfide bond formation with structural changes.
  • To assess the impact of folding and oxidation on MTX's bioactivity against Shaker B channels.

Main Methods:

  • Circular Dichroism (CD) analysis for secondary structure evolution.
  • Mass Spectrometry (MS) for disulfide bridge formation kinetics.
  • On-line electrophysiology in Xenopus oocytes to measure channel blocking efficacy during folding.

Main Results:

  • Stable secondary structures (alpha-helix and beta-sheet) formed sequentially over time.
  • Disulfide bridge formation occurred in parallel with structural changes.
  • Unexpectedly, sMTX showed potent blocking activity early in oxidation, with transient reductions later, before reaching full bioactivity.

Conclusions:

  • Disulfide bond formation is crucial for MTX's structural stabilization.
  • The process of disulfide bond formation can transiently alter MTX's three-dimensional structure and bioactivity.
  • These findings provide insights into the complex relationship between protein folding, structure, and function.

More Related Videos

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability09:49

Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability

Published on: April 2, 2015

Purification and Refolding to Amyloid Fibrils of (His)6-tagged Recombinant Shadoo Protein Expressed as Inclusion Bodies in E. coli09:43

Purification and Refolding to Amyloid Fibrils of (His)6-tagged Recombinant Shadoo Protein Expressed as Inclusion Bodies in E. coli

Published on: December 19, 2015

Related Concept Videos

Protein Folding01:49

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation which is critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.Protein Structure Is Critical to Its Biological FunctionProteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Folding01:25

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...