Sickle hemoglobin fibers: mechanisms of depolymerization
| Autor: | Suzanna Kwong, Scott M. Cohen, Robin W. Briehl, Gunjan Agarwal, Frank A. Ferrone, Robert Josephs, Jiang Cheng Wang |
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| Rok vydání: | 2002 |
| Předmět: |
Kinetics
Hemoglobin Sickle Anemia Sickle Cell Ligands Dissociation (chemistry) Diffusion Biopolymers Structural Biology Molecule Humans Protein Structure Quaternary Molecular Biology chemistry.chemical_classification Photolysis Chemistry Depolymerization Photodissociation Partial pressure Polymer Carbon Dioxide Microscopy Electron Atmospheric Pressure Biochemistry Models Chemical Biophysics Thermodynamics Hemoglobin |
| Zdroj: | Journal of molecular biology. 322(2) |
| ISSN: | 0022-2836 |
| Popis: | 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 approximately 1 microm 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. |
| Databáze: | OpenAIRE |
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