Biochemistry: Scientists Decode the Protective Element Sickle Cell Anemia Offers Against Malaria

nyt    Nov. 15, 2011  by Donald G. McNeil Jr.

Scientists believe they have finally figured out how the mutation that causes sickle cell anemia also protects against fatal malaria.

The trait is common in West Africa, where malaria is endemic. It is also common in people of West African ancestry: one in 12 black Americans have it. If the mutated gene is inherited from both parents, it can cause sickle cell anemia, in which red blood cells are twisted into oxygen-starved crescents, causing excruciating pain and sometimes leading to death. Inheriting the trait from one parent usually does not cause problems, and makes it unlikely the carrier will die of malaria, even if infected.

According to a new study by scientists from Germany and Burkina Faso, published online in the journal Science, when malaria parasites invade a red blood cell, they start twisting a protein, actin, from the inside of the cell membrane. The parasites reshape the actin into scaffolding that lets them mount a protein-shuttling structure called Maurer’s cleft.

The cleft pushes other “sticky” proteins through the membrane, which make the infected blood cell adhere to the walls of capillaries in the brain or other organs. This prevents the cell from being carried to the spleen, which spots and destroys abnormal blood cells — including those with parasites.

The researchers took electron microscope pictures of frozen red cells showing that those with the sickle cell trait are able to resist “actin mining.” Without that, there was no clinging and no sticky proteins, and the blood cell would be swept away to its doom, along with its squatters.