sickle-cell anemia

   how the substitution can have such a drastic effect on the sturcture of the protein?

[HFHS.M.D.L.M.]

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Dear Dustin:
Human red blood cells normally carry 3 types of hemoglobin , which differ in their protein structure . They are hemoglobin A , hemoglobin A2 , Hemoglobin F .Hemoglobin is a protein made of 4 amino acid chains . Hemoglobin A = 2a chains and 2b chains for example .In certain situations , a point mutation arises in the amino acid sequence of the DNA structure of the cell, resulting in the synthesis of unusual proteins by dictating the replacement of glutamic acid  at position 6 in the b-hemoglobin chain with valine . this substitution is on the surface of the molecule of hemoglobin and results in the tendency to polymerization , resulting in  semisolid crystalline structures called tactoids.
The more concentration of tactoids , the quicker the crystallization when exposed to a low oxygen environment.
Tactoids tend to ;
1.  decrease hemoglobin solubility
2.  change the shape of the red blood cell
3.  decrease deformability of the red cell.
These factors act together to change the red cell shape from a biconcave disc to a sickle shape.
With recurrent exposure to low oxygen in the blood, the red blood cells tend to acquire a sickled shape permanently . These deformed cells find their way to the spleen/liver where they get removed by phagocytosis , resulting in anemia .
Thank you for your question
Disclaimer ; this information is for educational purposes only
keywords : Hemoglobin S* , sickle cell anemia*(hematology)