The interaction mechanism and the functionality of yeast protein with hydrophilic and hydrophobic bioactive molecules

Yeast protein is a kind of yeast-source high-quality complete protein.The coexistence of bioactive molecules with yeast protein may influence its physicochemical property.This study discussed the interaction mechanism of yeast protein with two bioactive molecules,the hydrophobic curcumin and the hydrophilic epigallocatechin gallate(EGCG).Results indicated that curcumin and EGCG could interact with yeast protein with different binding stoichiometric numbers(0.8109±0.0695 and 2.7248±0.2422)and binding constants((3.8152±0.0078)×10^(4) and(1.1875±0.0440)×10^(5)),respectively.Both EGCG and curcumin decreased theα-helix content while increased theβ-sheet proportion,and co-binding remarkably reduced theα-helix proportion relative to the single ligand binding.The co-binding of these two compounds decreased the association extent of the yeast protein,which in turn reduced the diameter of yeast protein-EGCG-curcumin complex.The binding of EGCG with yeast protein improved the thermal stability of curcumin.Moreover,the co-binding improved the emulsification stability of yeast protein,and curcumin exhibited a more remarkable effect in improving the foamability.This work provides a theoretical basis for clarifying the interaction mechanisms of hydrophobic/hydrophilic molecules with yeast protein,and extends the potential applications of the novel fungus protein sources for food function enhancement and bioactive molecule stabilization.

Yeast Two-Hybrid Screening for Proteins that Interact with the Extracellular Domain of Amyloid Precursor Protein

Alzheimer＇s disease（AD） is a neurodegenerative disorder in which amyloid b plaques are a pathological characteristic. Little is known about the physiological functions of amyloid b precursor protein（APP）. Based on its structure as a type I transmembrane protein, it has been proposed that APP might be a receptor, but so far, no ligand has been reported. In the present study, 9 proteins binding to the extracellular domain of APP were identified using a yeast two-hybrid system. After confirming the interactions in the mammalian system, mutated PLP1,members of the FLRT protein family, and KCTD16 were shown to interact with APP. These proteins have been reported to be involved in Pelizaeus-Merzbacher disease（PMD） and axon guidance. Therefore, our results shed light on the mechanisms of physiological function of APP in AD, PMD, and axon guidance.

Inhibition of YIPF2 Improves the Vulnerability of Oligodendrocytes to Human Islet Amyloid Polypeptide

Excessive secretion of human islet amyloid polypeptide(hIAPP)is an important pathological basis of diabetic encephalopathy(DE).In this study,we aimed to investigate the potential implications of hIAPP in DE pathogenesis.Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function.We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus.In vitro assays revealed that oligodendrocytes,compared with neurons,were more prone to acidosis under exogenous hIAPP stimulation.Moreover,western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter(MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70.Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2(YIPF2,which modulates the transfer of CD147 to the cell membrane)as a significant target.Furthermore,YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice.These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding,potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.