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Allosteric effects of chloride ions at the intradimeric α 1 β 1 and α 2 β 2 interfaces of human hemoglobin
Author(s) -
Rujan Iulian N.,
Russu Irina M.
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10240
Subject(s) - chemistry , allosteric regulation , tetramer , hemoglobin , chloride , crystallography , ligand (biochemistry) , dimer , proton , ion , inorganic chemistry , stereochemistry , biochemistry , organic chemistry , physics , receptor , quantum mechanics , enzyme
The structural transition induced by ligand binding in human hemoglobin encompasses quaternary structure changes at the interfaces between the two αβ dimers. In contrast, the interfaces between α and β subunits within the same dimer (i.e., α 1 β 1 and α 2 β 2 interfaces) are structurally invariant. Previous work from this laboratory using NMR spectroscopy has identified four sites at the intradimeric α 1 β 1 and α 2 β 2 interfaces that, although structurally invariant, experience significant changes in the rates of proton exchange upon ligand binding. These sites are Hisα103(G10) and Hisα122(H5) in each α subunit of the hemoglobin tetramer. In the present work, we show that the proton exchange at the Hisα103(G10) sites is affected by the interactions of hemoglobin with chloride ions. Increasing concentrations of chloride ions at pH 6.45 and at 37°C enhance the exchange rate of the Hisα103(G10) N ε2 proton. The enhancement is greater in deoxygenated than in ligated hemoglobin. In the framework of the local unfolding model for proton exchange, these results suggest that the structural free energy and/or the proton transfer reactions at the Hisα103(G10) sites depend on the concentration of chloride ions. Therefore, the ligand‐induced changes at the Hisα103(G10) sites are modulated by the allosteric effect of chloride ions on hemoglobin. Proteins 2002;49:413–419. © 2002 Wiley‐Liss, Inc.