6) Consider the helical peptide shown below... (4 pts) Asp Fraction folded (pH 7

Question

6) Consider the helical peptide shown below... (4 pts) Asp Fraction folded (pH 7) 0.8 Lys Fraction folded (pH 13) 0.6 0.4 Asp 0.2 ys 20 40 Temp (deg. C) 60 80 100 pKa, Asp 4 pKa, Lys 9 Thermal denaturation experiments were carried out at pH 7 and pH 13. Explain why the melting temperature, Tm, decreases from pH 7 to pH 13. (Hint: consider the pKa values of Asp and Lys. How are the Asp/Lys salt bridges affected?) 7) Briefly explain how B-amyloid contributes to neurodegeneration in Alzheimer's disease. How does the Brichos domain reduce neural degradation? (Complete answer should include how fibrils are formed.) (4 pts)

Explanation / Answer

6)

Less folding will be there at pH 13 on temperature rise. Less folding means decrease in melting temperature; now the protein melts at low temperature.

Tm decreases from pH 7 to pH 13 because of the amino acids, Asp and Lys present in the protein.

Given pKa of Asp =4; and Lys=9.

Lower pKa means acid is stronger. pKa is directly proportional to pH. So, acid becomes weaker at higher pH.

Here pKa of the Asp and Lys is 4 and 9; when pH changes from 7 to 13, the protein becomes less strong acid. A weak acid will dissociate weakly in solution.

So, it will have less Tm; same is the case here. Tmdecreases from pH 7 to 13.

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