Journal article
Heterogeneous Nucleation in Sickle Hemoglobin: Experimental Validation of a Structural Mechanism
Biophysical journal, v 89(4), pp 2677-2684
Oct 2005
PMID: 16055526
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sickle hemoglobin polymerizes by two types of nucleation: homogeneous nucleation of aggregates in solution, and heterogeneous nucleation on preexisting polymers. It has been proposed that the same contact that is made in the interior of the polymer between the mutant site
β
6 and its receptor pocket on an adjacent molecule is the primary contact site for the heterogeneous nucleus. We have constructed cross-linked hybrid molecules in which one
β
-subunit is from HbA with Glu at
β
6, and the other is from HbS with a Val at
β
6. We measured solubility (using sedimentation) and polymerization kinetics (using laser photolysis) on cross-linked hybrids, and cross-linked HbS as controls. We find ∼4000 times less heterogeneous nucleation in the cross-linked AS molecules than in cross-linked HbS, in strong confirmation of the proposal. In addition, changes in stability of the nucleus support a further proposal that more than one
β
6 contact is involved in the homogeneous nucleus.
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Details
- Title
- Heterogeneous Nucleation in Sickle Hemoglobin: Experimental Validation of a Structural Mechanism
- Creators
- Maria A Rotter - Department of Physics, Drexel University, Philadelphia, Pennsylvania; andSuzanna Kwong - Department of Physics, Drexel University, Philadelphia, Pennsylvania; andRobin W Briehl - Department of Physics, Drexel University, Philadelphia, Pennsylvania; andFrank A Ferrone - Department of Physics, Drexel University, Philadelphia, Pennsylvania; and
- Publication Details
- Biophysical journal, v 89(4), pp 2677-2684
- Publisher
- Biophysical Society
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000232147600050
- Scopus ID
- 2-s2.0-25844504264
- Other Identifier
- 991014878533004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biophysics