Sickle Cell Anemia Sickle Cell anemia is an inherited red blood cell disorder. Normal red blood cells are round like doughnuts, and they move through small blood tubes in the body to deliver oxygen. Sickle red blood cells become hard, sticky and shaped like sickles used to cut wheat. When these hard and pointed red cells go through the small blood tube, they clog the flow and break apart. This can cause pain, damage and a low blood count, or anemia.

The origin of the disease is a small change in the protein hemoglobin The change in cell structure arises from a change in the structure of hemoglobin. A single change in an amino acid causes hemoglobin to aggregate.

The function of hemoglobin is to carry oxygen Biswal, B. K.Biswal, B. K., Vijayan, M.:Vijayan, M. Structures of Human Oxy- and Deoxyhaemoglobin at Different Levels of Humidity: Variability in the T State Acta Crystallogr., Sect.D 58 pp (2002) Hemoglobin A Normal hemoglobin has four subunits that each contain an oxygen binding site.

The origin of sickle cell anemia is a mutation in hemoglobin Padlan, E. A.Padlan, E. A., Love, W. E.: Refined crystal structure of deoxyhemoglobin S. I. Restrained least-squares refinement at 3.0-Å resolution. J Biol Chem 260 pp (1985)Love, W. E. Hemoglobin S A single mutation in hemoglobin results in a binding of one protein to another.

Hemoglobin is a carrier protein Lungs Tissues O2O2 CO 2 HbO 2 deoxy Hb (CO 2 )

Hemoglobin changes structure for efficient oxygen uptake and delivery HbO 2 deoxy Hb (CO 2 ) Strong binding state R state Weak binding state T state

Models for cooperativity

The cooperative R - T switch relies on iron displacement to communicate between  and  subunits Hemoglobin is composed of two  and two  subunits whose structures resemble myoglobin. Eaton et al. Nature Struct. Biol. 1999, 6, 351

The small change in hemoglobin structure leads to aggregation Normal hemoglobin (Hb A)Sickle cell hemoglobin (Hb S)  Subunits