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, using different biophysical and spectroscopic methods. We examined the hydrophobicity of the MSP domain using the fluorophore 1,8-ANS as a reporter for hydrophobic moieties. We found that the P56S mutation induces conformational changes within the MSP domain that eventually lead to an exposure of hydrophobic patches accessible to the solvent. Such exposure may affect the hydrophobic interaction network of the domain and consequently its structural packing.
