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Aggregation tendencies in the p53 family are modulated by backbone hydrogen bonds.

Sci Rep. 2016; 
CinoElio A,SoaresIaci N,PedroteMurilo M,de OliveiraGuilherme A P,SilvaJers
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Mutagenesis Services The p53 QM construct (M133L/V203A/ N239Y/N268D) was engineered by site-directed mutagenesis of the wt p53 construct (Genscript). Get A Quote

摘要

The p53 family of proteins is comprised of p53, p63 and p73. Because the p53 DNA binding domain (DBD) is naturally unstable and possesses an amyloidogenic sequence, it is prone to form amyloid fibrils, causing loss of functions. To develop p53 therapies, it is necessary to understand the molecular basis of p53 instability and aggregation. Light scattering, thioflavin T (ThT) and high hydrostatic pressure (HHP) assays showed that p53 DBD aggregates faster and to a greater extent than p63 and p73 DBDs, and was more susceptible to denaturation. The aggregation tendencies of p53, p63, and p73 DBDs were strongly correlated with their thermal stabilities. Molecular Dynamics (MD) simulations indicated ... More

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