Phospholipases a2 from Viperidae snakes: Differences in membranotropic activity between enzymatically active toxin
Narine A Ghazaryan1, Lusine Ghulikyan1, Arsen Kishmiryan1
1Orbeli Institute of Physiology, Orbely str. 22, 0019 Yerevan, Armenia.
Biochimica Et Biophysica Acta
|December 3, 2014
Summary
Snake venom phospholipases A2 (PLA2) interact differently with lipid membranes. Enzymes with aspartic acid cause vesicle deformation, while serine or lysine at position 49 induce aggregation and alter membrane fluidity.
Area of Science:
- Biochemistry
- Membrane Biophysics
- Toxicology
Background:
- Phospholipases A2 (PLA2) are enzymes found in snake venom.
- These enzymes play a role in venom's toxicity by interacting with cell membranes.
- The catalytic center's residue at position 49 influences PLA2 activity and membrane interaction.
Purpose of the Study:
- To investigate the interaction of different Viperidae family snake venom PLA2s with giant unilamellar vesicles (GUVs).
- To understand how variations in the catalytic center (Aspartic acid, Serine, or Lysine at position 49) affect PLA2-membrane interactions.
- To assess changes in membrane fluidity, lipid packing, and water penetration.
Main Methods:
- Utilized fluorescence microscopy to visualize PLA2-GUV interactions.
- Employed membrane fluorescent probes (ANS, LAUDRAN, PRODAN) to monitor membrane properties.
- Calculated the generalized polarization (GP) function to quantify water penetration into the lipid bilayer.
Main Results:
- PLA2 with aspartic acid at position 49 (D49 PLA2) caused oval deformation of GUVs.
- PLA2s with serine or lysine at position 49 (S49 PLA2, K49 PLA2) increased membrane fluorescence and induced GUV aggregation without shape change.
- All tested PLA2s decreased LAURDAN and PRODAN GP values, indicating increased water penetration, with K49 PLA2 showing less water penetration than D49 PLA2.
Conclusions:
- The residue at position 49 of Viperidae PLA2s significantly dictates their interaction mechanism with phospholipid bilayers.
- D49 PLA2 induces membrane disruption, while S49 and K49 PLA2s primarily cause membrane aggregation and alter fluidity.
- These findings contribute to understanding snake venom's complex effects on biological membranes.
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