Insight into "insoluble proteins" with pure water.

Many proteins are not refoldable and also insoluble. Previously no general method was available to solubilize them and consequently their structural properties remained unknown. Surprisingly, we recently discovered that all insoluble proteins in our laboratory, which are highly diverse, can be solubilized in pure water. Structural characterization by CD and NMR led to their classification into three groups, all of which appear trapped in the highly disordered or partially-folded states with a substantial exposure of hydrophobic side chains. In this review, I discuss our results in a wide context and subsequently propose a model to rationalize the discovery. The potential applications are also explored in studying protein folding, design and membrane proteins.