title: An osmolyte mitigates the destabilizing effect of protein crowding.
abstract: Most theories predict that macromolecular crowding stabilizes globular proteins, but recent studies show that weak attractive interactions can result in crowding-induced destabilization. Osmolytes are ubiquitous in biology and help protect cells against stress. Given that dehydration stress adds to the crowded nature of the cytoplasm, we speculated that cells might use osmolytes to overcome the destabilization caused by the increased weak interactions that accompany desiccation. We used NMR-detected amide proton exchange experiments to measure the stability of the test protein chymotrypsin inhibitor 2 under physiologically relevant crowded conditions in the presence and absence of the osmolyte glycine betaine. The osmolyte overcame the destabilizing effect of the cytosol. This result provides a physiologically relevant explanation for the accumulation of osmolytes by dehydration-stressed cells.
authors: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, 27599.
authors: Mohona
authors: M
authors: Sarkar
authors: Gary J
authors: GJ
authors: Pielak
mesh_terms: D001622:Betaine / Q000737:chemistry*; D003681:Dehydration; D003890:Desiccation; D009994:Osmolar Concentration; D010455:Peptides / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry*; D055550:Protein Stability; D013816:Thermodynamics
chemical_list: D010455:Peptides; D010940:Plant Proteins; C093336:chymotrypsin inhibitor 2; D001622:Betaine
keywords: amide proton exchange; macromolecular crowding; nonspecific interaction; osmolytes; protein stability