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Heterogeneous Nucleation in Sickle Hemoglobin: Experimental Validation of a Structural Mechanism
Journal article   Open access   Peer reviewed

Heterogeneous Nucleation in Sickle Hemoglobin: Experimental Validation of a Structural Mechanism

Maria A Rotter, Suzanna Kwong, Robin W Briehl and Frank A Ferrone
Biophysical journal, v 89(4), pp 2677-2684
Oct 2005
PMID: 16055526
url
https://doi.org/10.1529/biophysj.105.067785View
Published, Version of Record (VoR) Open

Abstract

Proteins
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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Collaboration types
Domestic collaboration
Web of Science research areas
Biophysics
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