SICKLE HEMOGLOBIN

Sickle hemoglobin differs from normal hemoglobin A by a single amino acid: valine replaces glutamate at position 6 on the surface of the beta chain sickle hemoglobin S. This creates a new hydrophobic spot (shown white).
When deoxygenated, a small hydrophobic patch appears on the surface sickle hemoglobin C (of both normal and sickle hemoglobin; shown as double white spot).
The hydrophobic spots stick to each other (excluding water) causing deoxygenated hemoglobin to aggregate into chains sickle hemoglobin SC.
In the hemoglobin crystal from which this structure was obtained, valine 6 (beta chain) bound to alanine 70 and leucine 88 (beta chain).
A close-up view. In a sickled red blood cel l, the valine 6 (beta chain) binds to a different hydrophobic patch (on the alpha chain, not shown).
The polymerized hemoglobin distorts red blood cells into an abnormal sickle shape. Heterozygotes have a mixture of normal hemoglobin A and mutant hemoglobin S. The hemoglobin A stops polymerization, preventing serious sickling.
The pure hemoglobin S in homozygotes polymerizes to a greater degree. Red cells lyse in homozygotes, producing the disease 'sickle cell anemia'.
Cickl0
Sickle hemoglobin, even in heterozygotes, confers resistance to one type of malaria. Through evolution, this selective advantage has led to a 40% incidence of sickle hemoglobin in some regions of Africa where malaria is endemic. References
Sicl1
Sickl2