#2,3,4 Deletion of Ser63 (i. the Ser residue found at the 63rd site) from the P0 protein causes Charcot-Marie-Tooth (CMT) disease, which is...

#2,3,4Deletion of Ser63 (i.e. the Ser residue found at the 63rd site) from the P0 protein causesCharcot-Marie-Tooth (CMT) disease, which is characterized by axonal demyelination inthe PNS.2. A visual examination of the cytoplasmic region of P0 reveals that in the case ofhistones, Arg and Lys are found at a much higher frequency compared to Glu andAsp. Why do you think that both P0 and histones are enriched with Arg and Lysresidues?3. Unlike the wild-type P0 protein, which is localized to the cell surface, the Ser63deletion P0 mutant is exclusively located at the ER. Based on these observations,what would be the most likely defect associated with the Ser63 deletion mutant?How would you design an experiment to test your hypothesis using culture cellsand the expression construct of wild-type and Ser63 deletion mutant of P0?4. The CMT disease phenotype is exacerbated in animals lacking IRE1p (one of theER UPR mediators). What does this result tell you about the pathogenesis ofCMT?