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Cyclotides insert into lipid bilayers to form membrane pores and destabilize the membrane through hydrophobic and phosphoethanolamine-specific interactions.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2012 Dec 21; Vol. 287 (52), pp. 43884-98. Date of Electronic Publication: 2012 Nov 05. - Publication Year :
- 2012
-
Abstract
- Cyclotides are a family of plant-derived circular proteins with potential therapeutic applications arising from their remarkable stability, broad sequence diversity, and range of bioactivities. Their membrane-binding activity is believed to be a critical component of their mechanism of action. Using isothermal titration calorimetry, we studied the binding of the prototypical cyclotides kalata B1 and kalata B2 (and various mutants) to dodecylphosphocholine micelles and phosphoethanolamine-containing lipid bilayers. Although binding is predominantly an entropy-driven process, suggesting that hydrophobic forces contribute significantly to cyclotide-lipid complex formation, specific binding to the phosphoethanolamine-lipid headgroup is also required, which is evident from the enthalpic changes in the free energy of binding. In addition, using a combination of dissipative quartz crystal microbalance measurements and neutron reflectometry, we elucidated the process by which cyclotides interact with bilayer membranes. Initially, a small number of cyclotides bind to the membrane surface and then insert first into the outer membrane leaflet followed by penetration through the membrane and pore formation. At higher concentrations of cyclotides, destabilization of membranes occurs. Our results provide significant mechanistic insight into how cyclotides exert their bioactivities.
- Subjects :
- Cyclotides metabolism
Ethanolamines metabolism
Hydrophobic and Hydrophilic Interactions
Lipid Bilayers metabolism
Oldenlandia metabolism
Plant Proteins metabolism
Protein Binding
Cyclotides chemistry
Ethanolamines chemistry
Lipid Bilayers chemistry
Oldenlandia chemistry
Plant Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 287
- Issue :
- 52
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23129773
- Full Text :
- https://doi.org/10.1074/jbc.M112.421198