Problem: In our discussion of the acid-base properties of individual amino acids, we indicated that most amino acids will be electrically neutral over a very broad range of pH values, so that the pI of an individual amino acid is a nearly meaningless quantity. By contrast, a full-length protein will be electrically neutral over a relatively narrow pH range — typically less than one pH unit. Thus the pI of a protein is a well-defined quantity. Why is this?

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Remember that the isoelectric point (pI) of a/an amino acid/polypeptide/protein is the pH values at which the net charge of the molecule is zero. To clarify a common misconception, pI is not just the average of the pKa values of the molecule's side chains, along with the pKa of the amino group in the N terminal and the carboxyl group in the C terminal.

In comparison with amino acids, proteins are usually made up of hundreds to several thousands of amino acids. And since its building blocks can only come from 20 different amino acids, repetition of amino acids in a sequence cannot be avoided.

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In our discussion of the acid-base properties of individual amino acids, we indicated that most amino acids will be electrically neutral over a very broad range of pH values, so that the pI of an individual amino acid is a nearly meaningless quantity. By contrast, a full-length protein will be electrically neutral over a relatively narrow pH range — typically less than one pH unit. Thus the pI of a protein is a well-defined quantity. Why is this?