Characterization of p56S insoluble aggregates. Analysis of the solubilization of the indicated mutants suggest that the oligomerization of VAP-B(P56S) is mediated mainly by the coiled-coil domain and that the GXXXG also contributes to VAP-B(P56S) oligomerization and consequently for the production… Continue Reading
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… Continue Reading
The P56S mutation induces the exposure of hydrophobic patches, thereby facilitating MSP oligomerization. To better understand how the P56S mutation enhances oligomerization of VAP-B(P56S), we characterized the folding properties of recombinant purified MSP domains of the WT and P56S mutant,… Continue Reading
Expression of the VAP-B(P56S) mutant in cultured cells results in the formation of insoluble protein aggregates. These aggregates might induce loss-of-function of wild-type VAP-B protein, gain of toxic function, or both.
The VAP-B is an integral endoplasmic reticulum (ER)-membrane protein implicated in the regulation of a wide range of cellular processes, including membrane trafficking, lipid transport and metabolism, and the unfolded protein response. In 2004, a dominant missense mutation (P56S) within the human VAP-Bgene… Continue Reading