Sickle hemoglobin fibers: Mechanisms of depolymerization

Gunjan Agarwal, Jiang Cheng Wang, Suzanna Kwong, Scott M. Cohen, Frank A. Ferrone, Robert Josephs, Robin W. Briehl

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)395-412
Number of pages18
JournalJournal of Molecular Biology
Volume322
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Sickle Hemoglobin
Carbon Monoxide
Ligands
Photolysis
Polymers
Pressure
Partial Pressure
Sickle Cell Anemia
Electrons

Keywords

  • Depolymerization
  • Fibers
  • Kinetics
  • Mechanism
  • Sickle hemoglobin

ASJC Scopus subject areas

  • Virology

Cite this

Agarwal, G., Wang, J. C., Kwong, S., Cohen, S. M., Ferrone, F. A., Josephs, R., & Briehl, R. W. (2002). Sickle hemoglobin fibers: Mechanisms of depolymerization. Journal of Molecular Biology, 322(2), 395-412. https://doi.org/10.1016/S0022-2836(02)00770-2

Sickle hemoglobin fibers : Mechanisms of depolymerization. / Agarwal, Gunjan; Wang, Jiang Cheng; Kwong, Suzanna; Cohen, Scott M.; Ferrone, Frank A.; Josephs, Robert; Briehl, Robin W.

In: Journal of Molecular Biology, Vol. 322, No. 2, 2002, p. 395-412.

Research output: Contribution to journalArticle

Agarwal, G, Wang, JC, Kwong, S, Cohen, SM, Ferrone, FA, Josephs, R & Briehl, RW 2002, 'Sickle hemoglobin fibers: Mechanisms of depolymerization', Journal of Molecular Biology, vol. 322, no. 2, pp. 395-412. https://doi.org/10.1016/S0022-2836(02)00770-2
Agarwal G, Wang JC, Kwong S, Cohen SM, Ferrone FA, Josephs R et al. Sickle hemoglobin fibers: Mechanisms of depolymerization. Journal of Molecular Biology. 2002;322(2):395-412. https://doi.org/10.1016/S0022-2836(02)00770-2
Agarwal, Gunjan ; Wang, Jiang Cheng ; Kwong, Suzanna ; Cohen, Scott M. ; Ferrone, Frank A. ; Josephs, Robert ; Briehl, Robin W. / Sickle hemoglobin fibers : Mechanisms of depolymerization. In: Journal of Molecular Biology. 2002 ; Vol. 322, No. 2. pp. 395-412.
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