Drepanocytes - sickle cells

3D Model

Haemoglobin is one of the most intensively studied proteins in the human body, hundreds of variants affecting its function have been identified. By far the most prevalent, affecting 6-7% of the world population, is mutation of the Glu6 residue which forms HbS, sickle cell haemoglobin. The mutation affects the surface charge of the protein, its deoxygenated form polymerises into a gel causing the characteristic shape change, called a drepanocyte. This is a reversible process when the cell is reoxygenated but repeated cycles of deformation gradually damage the cell, eventually leading to rupture. The sickle form gets trapped in capillaries leading to the vaso-occlusive crises experienced by affected individuals. The link to a protective effect against malaria is a classic example in population genetics however there are many other haemoglobin and erythrocyte mutations that also impair Plasmodium infection.