|Overview of Sickle Cell Hemoglobin, HbS|
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Under anaerobic conditions, sickle cell hemoglobin - HbS - polymerizes into highly elongated cables. In the red blood cell (RBC) such polymers distort its shape and suppleness resulting in a sickle-like appearance in contrast to the normal discoid appearance of normal RBC.
|For more information on blood cell morphology, see the histology web pages of Vanderbuilt University Medical School, the University of Leicester, and the University of Washington.|
The rigid sickle shape impairs the ability of the RBC to pass easily through small capillary openings. Only deoxyHbS, and not oxyHbS, polymerizes as is consistent with the fact that RBC sickling occurs in the capillaries where the O2 concentrations are relatively low and the deoxyHbS concentration is high. The sickle cell phenotype arises from a single mutation in the b-globin gene resulting in an amino acid substitution at the sixth residue of the b-chain with b-Val6 in HbS substituted for b-Glu6 in normal HbA. The hydrophobic b-Val6 sidechains are exposed on the surface of the two b-chains of HbS and they can fit into hydrophobic pockets created by the sidechains of b-Phe85 and b-Leu88 also on the b -chain surface. The spacing between these residues is such that deoxyHbS molecules self-associate and polymerize. However, the geometrical spacing between these residues is different for the oxyHbS conformer and it does not polymerize.
The proposed interactions between deoxyHbS molecules are illustrated by the structure of a of HbS dimer. These interactions are also nicely illustrated with a Kinemage graphic for HbS.
Spacefilling models comparing the key regions for these interactions on HbS can also be viewed by returning to section 4A4B of the outline.
Sickle Cell Hemoglobin HbA Compared to HbA
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© Duane W. Sears
May 9, 1997