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Effect of Signal Peptide on the Stability and Folding Kinetics of Maltose Binding Protein

Beena, K and Udgaonkar, Jayant B and Varadarajan, R (2004) Effect of Signal Peptide on the Stability and Folding Kinetics of Maltose Binding Protein. In: Biochemistry, 43 (12). pp. 3608-3619.

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While the role of the signal sequence in targeting proteins to specific subcellular compartments is well characterized, there are fewer studies that characterize its effects on the stability and folding kinetics of the protein. We report a detailed characterization of the folding kinetics and thermodynamic stabilities of maltose binding protein (MBP) and its precursor form, preMBP. Isothermal GdmCl and urea denaturation as a function of temperature and thermal denaturation studies have been carried out to compare stabilities of the two proteins. preMBP was found to be destabilized by about 2-6 kcal/mol (20-40%) with respect to MBP. Rapid cleavage of the signal peptide by various proteases shows that the signal peptide is accessible in the native form of preMBP. The observed rate constant of the major slow phase in folding was decreased 5-fold in preMBP relative to MBP. The rate constants of unfolding were similar at 25 °C, but preMBP also exhibited a large burst phase change in unfolding that was absent in MBP. At 10 °C, preMBP exhibited a higher unfolding rate than MBP as well as a large burst phase. The appreciable destabilization of MBP by signal peptide is functionally relevant, because it enhances the likelihood of finding the protein in an unfolded translocation-competent form and may influence the interactions of the protein with the translocation machinery. Destabilization is likely to result from favorable interactions between the hydrophobic signal peptide and other hydrophobic regions that are exposed in the unfolded state.

Item Type: Journal Article
Additional Information: The copyright belongs to American Chemical Society.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Anka Setty
Date Deposited: 27 May 2006
Last Modified: 19 Sep 2010 04:27
URI: http://eprints.iisc.ac.in/id/eprint/6916

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