Recombinant Echis disintegrins reveal distinct inhibitory profiles on platelet aggregation and endothelial cell migration
Disintegrins are snake venom toxins that bind integrins and modulate platelet aggregation and cell migration. Isolation from venom often yields insufficient quantities for comprehensive study, making recombinant expression essential for detailed toxin characterisation. Here, we produced and characterised four disintegrins from Echis coloratus and Echis ocellatus in Escherichia coli. These…
Snake venom toxins known as disintegrins have shown potential in modulating platelet aggregation and cell migration. Extracting these toxins from venom has proven challenging, necessitating recombinant expression for thorough analysis. Researchers successfully produced and analysed four disintegrins derived from two Echis snake species in E. coli.
These proteins possess unique integrin-binding motifs: EcDis_RGD, EoDis_RGD, EcDis_KGD, and EcDis_VGD. Functional tests on human platelet aggregation and endothelial cell migration revealed that RGD-containing disintegrins, particularly EcDis_RGD, displayed the strongest inhibition of platelet aggregation. EcDis_KGD showed weaker inhibitory effects, while EcDis_VGD demonstrated no detectable activity.
In endothelial cells, EcDis_RGD significantly hampered cell migration, whereas EoDis_RGD exhibited weaker anti-migratory effects. Neither EcDis_KGD nor EcDis_VGD significantly influenced wound closure. Importantly, EoDis_RGD replicated the antiplatelet activity of venom-purified ocellatusin, confirming the success of recombinant protein synthesis.
However, the corresponding PII-SVMP preparation showed reduced inhibitory effects, likely due to incomplete maturation of disintegrin species. These findings underscore the significance of both the integrin-binding motif and surrounding sequence context in governing disintegrin functionality, supporting the continued use of recombinant toxins in toxinology and as potential therapeutic leads.
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