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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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Chemical chaperone-mediated protein folding: stabilization of P22 tailspike folding intermediates by glycerol

Rajesh Mishra1 / Rajiv Bhat2 / Robert Seckler3

1Department of Biochemistry and Biology, Potsdam University, D-14476 Potsdam-Golm, Germany, Center for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India and Present address: Department of Chemistry, Physical Chemistry-I, University of Dortmund, D-44227 Dortmund, Germany.

2Center for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India

3Department of Biochemistry and Biology, Potsdam University, D-14476 Potsdam-Golm, Germany

Corresponding author

Citation Information: Biological Chemistry. Volume 388, Issue 8, Pages 797–804, ISSN (Online) 14316730, ISSN (Print) 14374315, DOI: 10.1515/BC.2007.096, August 2007

Publication History

Published Online:


Polyol co-solvents such as glycerol increase the thermal stability of proteins. This has been explained by preferential hydration favoring the more compact native over the denatured state. Although polyols are also expected to favor aggregation by the same mechanism, they have been found to increase the folding yields of some large, aggregation-prone proteins. We have used the homotrimeric phage P22 tailspike protein to investigate the origin of this effect. The folding of this protein is temperature-sensitive and limited by the stability of monomeric folding intermediates. At non-permissive temperature (≥35°C), tailspike refolding yields were increased significantly in the presence of 1–4 m glycerol. At low temperature, tailspike refolding is prevented when folding intermediates are destabilized by the addition of urea. Glycerol could offset the urea effect, suggesting that the polyol acts by stabilizing crucial folding intermediates and not by increasing solvent viscosity. The stabilization effect of glycerol on tailspike folding intermediates was confirmed in experiments using a temperature-sensitive folding mutant protein, by fluorescence measurements of subunit folding kinetics, and by temperature up-shift experiments. Our results suggest that the chemical chaperone effect of polyols observed in the folding of large proteins is due to preferential hydration favoring structure formation in folding intermediates.

Keywords: aggregation; bacteriophage P22; folding kinetics; misfolding; osmolyte; tailspike protein

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