Potential mechanisms underlying the aggregation and motor neurodegeneration of VAP-B(P56S) mutant. The Lev’s lab found that the P56S mutation enhances the exposure of hydrophobic patches which together with the coiled-coil domain facilitate VAP-B(P56S) oligomerization and aggregation thereby preventing the binding of FFAT protein. Hence, VAP-B(P56S) aggregates induce both loss-of-function of wild-type VAP-B protein and gain of toxic function.
