The Effect of the P56S on FFAT Binding

Oligomerization of VAP-B(P56S) prevents binding of FFAT proteins. We found that the conformational changes of MSP domain of P56S mutant have no direct effect on FFAT-binding. Rather, they enhance VAP-B(P56S) oligomerization driven by the combined contributions of the coiled-coil and the transmembrane domains, thereby preventing accessibility to FFAT-binding site, facilitating the production of VAP-B(P56S) insoluble aggregates and consequently its neurotoxicity.

Slide #10 From Sima Lev's presentation - VAP-B and its role in Amyotrophic lateral sclerosis
From prof. Sima Lev’s presentation –VAP-B and its role in Amyotrophic lateral sclerosis

Sima Lev Web Team

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