Question

Please answer the following question:

Sickle-cell anemia is a disease in which one subunit of hemoglobin protein contains a single amino acid substitution: a Glu (glutamic acid residue is replaced with Val (valine) Examine the structures of Glu and Val and your answers to the previous two questions. How do you expect each of the following to be affected in the hemoglobin protein of a sickle-cell anemia patient compared to the hemoglobin protein of a normal individual?

1. Primary protein structure

2. Secondary protein structure

3. Tertiary protein structure

4. Quaternary protein structure

5. Protein function

Answer 1

In primary and secondary structure there is no such big difference just glutamic acid is replaced with valine.

The interaction between Val 6 on one chain of one hemoglobin molecule and a hydrophobic patch formed by Phe 85 and Leu 88 on a chain of another deoxygenated hemoglobin molecule leads to hemoglobin aggregation.

In quaternary structure, the alpha subunits do not fold properly so RBC becomes sickle-shaped.

The association of two wild-type a-globin subunits with two mutant ß-globin subunits forms hemoglobin S, which polymerizes under low oxygen conditions causing distortion of red blood cells and a tendency for them to lose their elasticity. New erythrocytes are quite elastic, which allows the cells to deform to pass through capillaries. Often a cycle occurs because as the cells sickle, they cause a region of low oxygen concentration which causes more red blood cells to sickle. Repeated episodes of sickling cause loss of this elasticity and the cells fail to return to normal shape when oxygen concentration increases. These rigid red blood cells are unable to flow through narrow capillaries, causing vessel occlusion and ischemia.

Normal hemoglobin is called hemoglobin A, but people with the sickle cell disease have only hemoglobin S, which turns normal, round red blood cells into abnormally curved (sickle) shapes. Normally, a person inherits two genes (one from each parent) that produce beta-globin, a protein needed to produce normal hemoglobin (hemoglobin A). A person with sickle cell trait inherits one normal beta-globin gene (hemoglobin A) and one defective gene (hemoglobin S). People with sickle cell trait rarely have symptoms due to the condition because they also have some normal hemoglobin. However, they can pass the sickle cell trait to their children, and in rare cases, exercise-induced dehydration or exhaustion can cause healthy red blood cells to turn sickle-shaped, which can cause death. A person in whom both beta-globin genes are abnormal (they produce hemoglobin S) has sickle cell disease, which can cause serious problems. Both parents must have either the sickle cell trait or the disease itself for a child to have sickle cell disease. People who have the sickle cell trait have reduced susceptibility to malaria, due to natural selection for the heterozygote advantage. However, people with the sickle cell trait can still contract severe cases of malaria.