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Polymerization and Three Dimensional Reconstruction of Deoxy-Sickle Cell Hemoglobin Fibers in High and Low Phosphate Buffers

Published online by Cambridge University Press:  02 July 2020

Zhiping Wang ,
Gregory Kishchenko ,
Yimei Chen  and
Robert Josephs
Zhiping Wang
Affiliation:
Department of Molecular Genetics and Cell Biology. The University of Chicago, Chicago, IL60637
Gregory Kishchenko
Affiliation:
Department of Molecular Genetics and Cell Biology. The University of Chicago, Chicago, IL60637
Yimei Chen
Affiliation:
Department of Molecular Genetics and Cell Biology. The University of Chicago, Chicago, IL60637
Robert Josephs
Affiliation:
Department of Molecular Genetics and Cell Biology. The University of Chicago, Chicago, IL60637
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Extract

The amino acid substitution (B Glu → G6 Val) results in the conversion of Hemoglobin A (HbA) to sickle cell hemoglobin(HbS) which is responsible for sickle cell disease. Under physiological conditions this substitution causes a reduction of the solubility of HbA from about 340 mg/ml to 165 mg/ml (for HbS). One consequence of the reduction in solubility is that HbS polymerizes to form long fiber like structures about 240Å in diameter. The formation of these fibers causes sickle cell disease. The fibers fill the red cell and cause it to assume a characteristic sickle shape. More significantly the fibers cause the red cell to become rigid and, as a result, sickled cells can block blood flow in the capillaries. Understanding the polymerization process in detail is important for understanding the pathophysiology of sickle cell disease and for developing a specific therapy that could be used in its treatment.

Type
Electron Cryomicroscopy of Macromolecules
Information
Microscopy and Microanalysis , Volume 6 , Issue S2: Proceedings: Microscopy & Microanalysis 2000, Microscopy Society of America 58th Annual Meeting, Microbeam Analysis Society 34th Annual Meeting, Microscopical Society of Canada/Societe de Microscopie de Canada 27th Annual Meeting, Philadelphia, Pennsylvania August 13-17, 2000 , August 2000 , pp. 240 - 241
Copyright
Copyright © Microscopy Society of America

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