I can offer a highly speculative answer. Many water-soluble proteins have a hydrophobic core and a hydrophilic exterior. They tend denature in organic solvents because the hydrophobic side-chains can now be exposed to solvent, and one can think of the protein as turning inside out. Whether this is in fact what happens, I don't know. Gary Pielak studies proteins in vivo by NMR, and possibly he would have some experimental data or better insight.