Shown below is the amino acid sequence of human Islet Amyloid Polypeptide(hIAPP)

Question

Shown below is the amino acid sequence of human Islet Amyloid Polypeptide(hIAPP), a peptide hormone that plays a role in metabolism and is thought to play a role in the pathogenesis of type 2 diabetes.

KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY

Question:

A. At physiological pH how many of the side chains in hIAPP are charged?

B. Taking into consideration the charged state of N and C termini, calculate the overall charge of hIAPP at physiological pH. Show your reasoning

C. What hydrophobic residues are present in hIAPP?

D. What hydrophillic residues are present in hIAPP?

Explanation / Answer

A. Three side chains are present in hIAPP

B. There are three amino acids that have basic side chains at physiological pH i.e arginine (Arg), lysine (Lys), and histidine (His). Two amino acids have acidic side chains at physiological pH and these are aspartic acid or aspartate (Asp) and glutamic acid or glutamate (Glu).

In hIAPP there are three basic amino acids namely Arginine (R), Lysine (K) and Histidine (H); and one negative charge at C-terminus due to Y

Histidine has a pKa close to our physiological pH (pH = 7, pKa = 6.0 from the table in Stryer). Using the Henderson Hasslebach equation, we can determine that about 9% of the histidines have a positive charge; to the total contribution form histidine is 9% of +1 = +0.09

Hence, total charge = K (+2) + R (+1) + H + Y = (+2.0) + (+1.0) + (+0.09) + (-1) = +2.09

C. Hydrophobic amino acids in hIAPP: A, I, L, F, V and G

D. Hydrophilic amino acids in hIAPP: Q, N, H, S, T, Y and C

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