Folding of the disulfide-bonded beta-sheet protein tendamistat: rapid two-state folding without hydrophobic collapse

Journal of Molecular Biology
N SchönbrunnerT Kiefhaber

Abstract

We investigated the reversible folding and unfolding reactions of the small 74 amino acid residue protein tendamistat. The secondary structure of tendamistat contains only beta-sheets and loop regions and the protein contains two disulfide bonds. Fluorescence-detected refolding kinetics of tendamistat (disulfide bonds intact) comprise of a major rapid fast reaction (tau = 10 ms in water) and two minor slow reactions. In the fast reaction 80% of the unfolded molecules are converted to native protein. The two slow reactions are part of a parallel slow folding pathway. On this pathway the rate-limiting step in the formation of native molecules is cis to trans isomerization of at least one of the three trans Xaa-Pro peptide bonds. This reaction is catalyzed efficiently by the enzyme peptidyl-prolyl cis-trans isomerase. Comparison of kinetic data with equilibrium unfolding transitions shows that the fast folding pathway follows a two-state process without populated intermediate states. Additionally, various sensitive tests did not detect any rapid chain collapse during tendamistat folding prior to the acquisition of the native three-dimensional structure. These results show that pre-formed disulfide bonds do not prevent efficient an...Continue Reading

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Citations

May 23, 2001·Protein Science : a Publication of the Protein Society·J S ReaderS E Radford
Sep 24, 1999·Biological Chemistry·O Bieri, T Kiefhaber
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·O BieriT Kiefhaber
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·G PappenbergerT Kiefhaber
Dec 28, 1999·Journal of Molecular Biology·D A Debe, W A Goddard
Sep 15, 1998·Journal of Molecular Biology·D K Klimov, D Thirumalai
Feb 5, 2000·Journal of Molecular Biology·A M Bonvin, W F van Gunsteren
Jun 15, 2011·Physical Chemistry Chemical Physics : PCCP·David De Sancho, Victor Muñoz
Oct 20, 2000·The Journal of Biological Chemistry·D SamuelC Yu
Nov 16, 2013·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Hüseyin KayaHue Sun Chan
Mar 10, 2001·Journal of Molecular Biology·A Bachmann, T Kiefhaber
Jun 19, 2003·Journal of the American Chemical Society·Jovencio HilarioTimothy A Keiderling
Feb 21, 1998·Biochemistry·N A Van NulandC M Dobson

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