Journal article
Dissecting the Energies that Stabilize Sickle Hemoglobin Polymers
Biophysical journal, v 105(9), pp 2149-2156
05 Nov 2013
PMCID: PMC3824546
PMID: 24209860
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sickle hemoglobin forms long, multistranded polymers that account for the pathophysiology of the disease. The molecules in these polymers make significant contacts along the polymer axis (i.e., axial contacts) as well as making diagonally directed contacts (i.e., lateral contacts). The axial contacts do not engage the mutant beta 6 Val and its nonmutant receptor region on an adjacent molecule, in contrast to the lateral contacts which do involve the mutation site. We have studied the association process by elastic light scattering measurements as a function of temperature, concentration, and primary and quaternary structure, employing an instrument of our own construction. Even well below the solubility for polymer formation, we find a difference between the association behavior of deoxy sickle hemoglobin molecules (HbS), which can polymerize at higher concentration, in comparison to COHbS, COHbA, or deoxygenated Hemoglobin A (HbA), none of which have the capacity to form polymers. The nonpolymerizable species are all quite similar to one another, and show much less association than deoxy HbS. We conclude that axial contacts are significantly weaker than the lateral ones. All the associations are entropically favored, and enthalpically disfavored, typical of hydrophobic interactions. For nonpolymerizable Hemoglobin, Delta H-o was 35 +/- 4 kcal/mol, and Delta S was 102.7 +/- 0.5 cal/(mol-K). For deoxyHbS, Delta H-o was 19 +/- 2 kcal/mol, and Delta S was 56.9 +/- 0.5 cal/(mol-K). The results are quantitatively consistent with the thermodynamics of polymer assembly, suggesting that the dimer contacts and polymer contacts are very similar, and they explain a previously documented significant anisotropy between bending and torsional moduli. Unexpectedly, the results also imply that a substantial fraction of the hemoglobin has associated into dimeric species at physiological conditions.
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Details
- Title
- Dissecting the Energies that Stabilize Sickle Hemoglobin Polymers
- Creators
- Yihua Wang - Drexel Univ, Dept Phys, Philadelphia, PA 19104 USAFrank A. Ferrone - Drexel University, Physics
- Publication Details
- Biophysical journal, v 105(9), pp 2149-2156
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- National Heart, Lung and Blood Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000326858400025
- Scopus ID
- 2-s2.0-84887379457
- Other Identifier
- 991021863003104721
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- Web of Science research areas
- Biophysics