Template:NYMU-2015project-drylab-FYVE

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FYVE inhibition

This model was designed to investigate the competitive binding between FYVE protein domain and PI3P. Before we construct the circuit with FYVE, we have to determine whether the affinity between FYVE and PI3P is strong enough to compete with Avr3 effector protein secreted by P. infestans. We characterize this agonist-antagonist competition model by Gaddum-Schild equation. This model consists of two parts: monomeric FYVE and dimeric FYVE. According to paper research, monomeric FYVE is not so stable but the affinity of both monomeric and dimeric FYVE is quite high. The model is used to determine how much FYVE protein domain we should link with a linker so that the affinity of FYVE will be high enough to compete with Avr3.

Result

Conclusion

As we can see in the models dimeric FYVE is not only more stable but also have higher affinity to compete with avr3, the effector protein secreted by p.infestans. To create FYVE protein domain with higher affinity, we can link as much FYVE domain artificially as we want. However, it takes a lot of time to add a linker protein between FYVE and connect two FYVE together. Moreover, the longer the FYVE is, the longer it takes for the palnt to degrade the protein we created, which might have a negative impact to the potato. By constructing this model, we can find out the simplest way to create a competitive inhibitor and save the time for trial and error.

Parameters

Kd monomeric FYVE	Dissociation constant of monomeric FYVE	420	nM	Structural Basis for Endosomal Targeting by FYVE Domains
Kd dimeric FYVE	Dissociation constant of dimeric FYVE	38	nM	Phosphatidylinositol 3-Phosphate Induces the Membrane Penetration of the FYVE Domains of Vps27p and Hrs
Kd Avr3	Dissociation constant of Avr3	210	nM	External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectors into Plant and Animal Host Cells

Reference:

1. Structural Basis for Endosomal Targeting by FYVE Domains
2. Phosphatidylinositol 3-Phosphate Induces the Membrane Penetration of the FYVE Domains of Vps27p and Hrs
3. External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectors into Plant and Animal Host Cells