Journal article
Sickle Hemoglobin Fibers: Mechanisms of Depolymerization
Journal of molecular biology, v 322(2), pp 395-412
2002
PMID: 12217699
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Abstract
We examined the depolymerization of hemoglobin (Hb) S fibers in the presence of CO by using photolysis of COHbS to create and isolate individual fibers, then removing photolysis to induce depolymerization. Depolymerization occurs at two sites, fiber ends and fiber sides, with different kinetics and by different mechanisms. At low partial pressure of CO (pCO), end-depolymerization is dominant, proceeding at ∼1
μm
s
−1, whereas at high pCO fibers vanish very rapidly, in much less than one second, by side-depolymerization. Each kind of depolymerization could occur by a ligand-independent path, in which deoxyHb depolymerizes and then is prevented from returning to the polymer by liganding with CO, or by a ligand-dependent path in which CO binds to the polymer inducing dissociation of the newly liganded molecules from it. We find that ligand-independent depolymerization is the dominant path for end-depolymerization and ligand-dependent depolymerization dominates, at least at high pCO, for side-depolymerization. On the basis of our kinetic results and electron micrographs of depolymerizing fibers, we propose a model for side-depolymerization in which a hole is nucleated by cooperative loss of a few molecules from fiber sides, followed by rapid depolymerization from the newly created fiber ends abutting the hole. Potential significance of these results for the pathophysiology of sickle cell disease is discussed.
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Details
- Title
- Sickle Hemoglobin Fibers: Mechanisms of Depolymerization
- Creators
- Gunjan Agarwal - Department of Physiology, Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461-1975 Bronx, NY, USAJiang Cheng Wang - Department of Physiology, Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461-1975 Bronx, NY, USASuzanna Kwong - Department of Physiology, Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461-1975 Bronx, NY, USAScott M Cohen - Department of Physics, Duquesne University, Pittsburgh, PA 15282, USAFrank A Ferrone - Department of Physics, Drexel University, Philadelphia, PA 19104, USARobert Josephs - Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USARobin W Briehl - Department of Physiology, Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461-1975 Bronx, NY, USA
- Publication Details
- Journal of molecular biology, v 322(2), pp 395-412
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000178230500012
- Scopus ID
- 2-s2.0-0036384302
- Other Identifier
- 991014877712804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology