Inhibition of protein aggregation in vitro and in vivo by a natural osmoprotectant.

摘要: Small organic molecules termed osmolytes are harnessed by a variety of cell types in wide range organisms to counter unfavorable physiological conditions that challenge protein stability and function. Using well characterized reporter system we developed allow vivo observations, have explored how the osmolyte proline influences aggregation model aggregation-prone protein, P39A cellular retinoic acid-binding protein. Strikingly, find natural abrogates both vitro (in an Escherichia coli expression system). Importantly, also prevented constructs containing exon 1 huntingtin with extended polyglutamine tracts. Although compatible known stabilize native state, our results point destabilizing effect on partially folded states early aggregates solubilizing state. Because is believed act through combination solvophobic backbone interactions favorable side-chain not specific particular sequence or structure, observed likely be general. Thus, may protective against biomedically important hallmarks several late-onset neurodegenerative diseases including Huntington’s, Alzheimer’s, Parkinson’s. In addition, these should practical importance because they enable at higher efficiency under where competes proper folding.