Human neuronal tau-40 (htau-40) has been used to study denaturation and renaturation of rabbit muscle D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12). Inactivation of GAPDH incubated with tau was more distinguishably detected than that of control GAPDH during thermal and guanidine hydrochloride (GdnHCl) denaturation. However, tau did not influence the activity of GAPDH at room temperature or in solution without GdnHCl. A marked change in both the emission intensity and emission maximum of the intrinsic fluorescence at 335nm of GAPDH with tau was observed when GdnHCl concentration was 0.8M, but that of the control without tau occurred in 1.2M GdnHCl. The first-order rate of the decrease in the fluorescence intensity of the enzyme with tau was approximately twice as great as that of GAPDH without tau. Kinetics of inactivation of GAPDH with tau in 0.2M GdnHCl was a monophasic procedure, instead of the biphasic procedure followed by the control, as described before [He, Zhao, Yan and Li (1993) Biochim. Biophys. Acta 1163, 315–320]. Similar results were obtained when the enzyme was thermally denatured at 45°C. It revealed that tau bound to the denatured GAPDH but not the native molecule. On the other hand, tau suppressed refolding and reactivation of GAPDH when this enzyme was reactivated by dilution of GdnHCl solution. Furthermore, tau improved the aggregation of the non-native GAPDH in solutions. It suggested that tau acted in an anti-chaperone-like manner towards GAPDH in vitro. However, tau lost that function when it was aggregated or phosphorylated by neuronal cdc2-like protein kinase. It showed that tau's anti-chaperone-like function depended on its native conformation.

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