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Heparin Binding Stabilizes the Membrane-bound Form of Cobra Cardiotoxin
- Source :
- Journal of Biological Chemistry. 277:2666-2673
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- It has been shown previously that the long chain fragments of heparin bind to the beta-strand cationic belt of the three-finger cobra cardiotoxin (or cytotoxin, CTX) and hence enhance its penetration into phospholipid monolayer under physiological ionic conditions. By taking lysophosphatidylcholine (LPC) micelles as a membrane model, we have shown by (1)H NMR study that the binding of heparin-derived hexasaccharide (Hep-6) to CTX at the beta-strand region can induce conformational changes of CTX near its membrane binding loops and promote the binding activity of CTX toward LPC. The Fourier-transform infrared spectra and NMR nuclear Overhauser effect of Hep-6.CTX and CTX.LPC complex in aqueous buffer also supplemented the aforementioned observation. Thus, the detected conformational change may presumably be the result of structural coupling between the connecting loops and its beta-strands. This is the first documentation of results showing how the association of hydrophilic carbohydrate molecules with amphiphilic proteins can promote hydrophobic protein-lipid interaction via the stabilization of its membrane-bound form. A similar mechanism involving tripartite interactions of heparin, protein, and lipid molecules may be operative near the extracellular matrix of cell membranes.
- Subjects :
- Models, Molecular
Conformational change
Magnetic Resonance Spectroscopy
Protein Conformation
Stereochemistry
Phospholipid
Cobra Cardiotoxin Proteins
Plasma protein binding
Nuclear Overhauser effect
Biochemistry
Protein Structure, Secondary
chemistry.chemical_compound
Protein structure
Animals
Elapidae
Binding site
Molecular Biology
Micelles
Phospholipids
Binding Sites
Dose-Response Relationship, Drug
Heparin
Cell Membrane
Lysophosphatidylcholines
Cell Biology
Nuclear magnetic resonance spectroscopy
Lipids
Extracellular Matrix
Kinetics
Spectrometry, Fluorescence
Membrane
chemistry
Protein Binding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 277
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....2b6e18a7ec54f577f039b0fde4e3fe4c