Below is the protein sequence for the beta subunit of human

Below is the protein sequence for the beta subunit of human hemoglobin (using the one letter abbreviations for amino acids). Use it to answer the following questions.

1. Write the order of the LAST 10 amino acids in this protein.

2. For each of the LAST 10 amino acids, tell one other amino acid that it would favorably interact with (i.e. could form a bond with).

3. In sickle cell anemia, the first glutamate (E) is mutated to valine (V). Propose a hypothesis on how this change of amino acid will affect the folding of the hemoglobin protein and why the hemoglobin function will change.

MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFG KEFTPPVQAAYQKVVAGVANALAHKYH

Solution

(1)NH2- Leu - Val - Cys - Val - Leu - Ala - His - His - Phe - Gly –COOH

(2)

Favorably interacts with

Leu

Tyr or valine

Val

Leu

Cys

Cys, Met

Ala

Glu, Asp

His

Glu, Asp

Phe

Try, Met

Gly

Phe, Lys

(3)

The valine substitution at the place of glutamic acid will result in a change of only one nitrogen base in the genetic code. But the 3D structure of the protein is decided by its primary sequence encoded by the gene. Any slight change in the gene will result in an alteration in the primary sequence of protein, thus it affects the folding and 3D structure of that polypeptide.

As we know our Hb protein is made up of four polypeptide chains, 2 alpha (141 amino acids long) and 2 beta (146 amino acids long). Based on the amino acid composition and the interaction among these amino acids, the protein will fold to attain its 3D structure.

The ability hydrophilic side chain of glutamic acid found in one of the beta polypeptide chains in the hemoglobin will allow the hemoglobin to remain in dispersed form within our RBCs.

But when glutamic acid was replaced by valine, the isopropyl group of valine which is a non-polar hydrophobic groups will not form regular hydrogen bonds with water and but instead will go and react with non polar residues like leucine and phenylalanine and thus protein will try to avoid water and thus will try to stabilize itself by interacting with other hydrophobic residues finally leading to the formation of long protein filaments and this will give the shape of sickle and thus these will try to clog the narrow capillaries. Like this one amino acid substitution will brings a drastic change in the way the protein folds and works.