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Cu2+ SPEEDS UP MAUROTOXIN OXIDATIVE FOLDING
- Source :
- Journal of Biomolecular Structure and Dynamics, Journal of Biomolecular Structure and Dynamics, 2008, 26 (1), pp.75-82
- Publication Year :
- 2008
- Publisher :
- HAL CCSD, 2008.
-
Abstract
- International audience; Maurotoxin (MTX) is a 34-mer scorpion toxin cross-linked by four disulphide bridges that acts on various K+ channel types. It folds according to an alpha/beta scaffold, i.e., a helix connected to a two stranded beta-sheet by two disulphide bridges. In a former study, various parameters that affect the oxidation and folding of the reduced form of synthetic MTX were investigated in vitro. It was found that MTX achieves its final 3-D structure by evolving over time through a series of oxidation intermediates, from the least to the most oxidized species. MTX oxidative intermediates can be studied by iodoacetamide alkylation of free cysteine residues followed by mass spectrometry analysis. Here, we have analysed the effect of Cu2+ (0.1 to 50 mM) on the kinetics of MTX oxidative folding and found that it dramatically speeds up the formation of the four-disulphide bridged, native-like, MTX (maximal production within 30 minutes instead of > 60 hours). This catalysing effect of Cu2+ was found to be concentration-dependent, reaching a plateau at 10 mM copper ions. Cu2+ was also found to prevent the slow transition of a three disulphide-bridged MTX intermediate towards the final four disulphide-bridged product (12% of total MTX). The data are discussed in light of the potential effects of Cu2+ on MTX secondary structure formation, disulphide bridging and peptidyl prolyl cis-trans isomerization.
- Subjects :
- musculoskeletal diseases
MESH: Oxidation-Reduction
scorpion toxin
[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
MESH: Protein Folding
MESH: Protein Structure, Secondary
MESH: Amino Acid Sequence
Cu2+
MESH: Circular Dichroism
disulphide bridging
MESH: Scorpion Venoms
MESH: Mice, Inbred C57BL
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
MESH: Animals
MESH: Disulfides
MESH: Mice
mass spectrometry
MESH: Neurotoxins
MESH: Iodoacetamide
MESH: Alkylation
MESH: Molecular Sequence Data
MESH: Copper
maurotoxin
MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
oxidative folding
Subjects
Details
- Language :
- English
- ISSN :
- 07391102 and 15380254
- Database :
- OpenAIRE
- Journal :
- Journal of Biomolecular Structure and Dynamics, Journal of Biomolecular Structure and Dynamics, 2008, 26 (1), pp.75-82
- Accession number :
- edsair.od......1398..a281c3658fbdef20657a938eae9d07b8