Nir2, CERT and OSBP are three lipid-transfer proteins containing an FFAT motif, interact with VAP-A/B and localize to the Golgi apparatus at steady-state. Targeting of OSBP and CERT to the Golgi is mediated by their PH domains which bind PI4P… Continue Reading
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… Continue Reading
Prof. Sima Lev’ team showed that the three Nir proteins interact with VAP-B, but each interaction affects the structural integrity of the ER membranes differently. Whereas the Nir2-VAP-B interaction induces the formation of stacked ER membrane arrays as demonstrated by… Continue Reading
Prof. Sima Lev’ team showed that the Nir2 protein mainly localizes to the Golgi in interphase cells, and isolated the integral ER-membrane protein VAP-B as Nir2-interacting protein. They showed that Nir2-VAP-B interaction is mediated by the FFAT (EFFDAxE) motif within… Continue Reading
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
The N-terminal cytoplasmic MSP (major sperm protein) domain of VAP-B consistes of 125 amino acids (aa), and a coiled-coil domain (CCD) of ~50 aa. Proline 56 resides within a highly conserved sequence of 16 aa in the MSP domain in… Continue Reading
Potential mechanisms underlying the aggregation and motor neurodegeneration of VAP-B (P56S) mutant.
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.