Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-10-31T22:51:42.613Z Has data issue: false hasContentIssue false

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
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
Get access

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
Copyright
Copyright © Microscopy Society of America

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Vassar, R. J., Potel, M. J., and Josephs, R. J., J. Mol. Biol. 157(1982)395CrossRefGoogle Scholar
2.Dykes, G. W., Crepeau, R. H. and Edelstein, S. J., J. Mol. Biol. 130(1979)451CrossRefGoogle Scholar
3.Carragher, B., Bluemke, D. A., Gabriel, B., Potel, M. J. and Josephs, R. J., J. Mol. Biol. 199(1988)315CrossRefGoogle Scholar
4.Dean, J. and Schechter, A. N., New England J. Med. 299(1978)752, 804, 863CrossRefGoogle Scholar
5.Adachi, K. and Asakura, T., J. Biol. Chem. 254(1979)12273Google Scholar
6.Adachi, K. and Asakura, T., Blood Cell. 8(1982)213Google Scholar
7. This work was supported by NIH grants HL 22654 and HL 58512Google Scholar