Kinetic instability of p53 core domain mutants: implications for rescue by small molecules
Oncogenic mutations in the tumor suppressor protein p53 are found mainly in its DNA-
binding core domain. Many of these mutants are thermodynamically unstable at body
temperature. Here we show that these mutants also denature within minutes at 37° C. The
half-life (t ½) of the unfolding of wild-type p53 core domain was 9 min. Hot spot mutants
denatured more rapidly with increasing thermodynamic instability. The highly destabilized
mutant I195T had at ½ of less than 1 min. The wild-type p53-(94–360) construct, containing …
binding core domain. Many of these mutants are thermodynamically unstable at body
temperature. Here we show that these mutants also denature within minutes at 37° C. The
half-life (t ½) of the unfolding of wild-type p53 core domain was 9 min. Hot spot mutants
denatured more rapidly with increasing thermodynamic instability. The highly destabilized
mutant I195T had at ½ of less than 1 min. The wild-type p53-(94–360) construct, containing …
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