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. 1978 Jan;75(1):311–314. doi: 10.1073/pnas.75.1.311

Self-association of hemoglobin βSH chains is linked to oxygenation

Roland Valdes Jr 1, Gary K Ackers 1,*
PMCID: PMC411237  PMID: 24215

Abstract

Self-association of unliganded βSH chains into tetramers (4 β1 [unk] β4) is experimentally found to be energetically less favorable (ΔG0 = -19.05 ± 0.30 kcal) than the corresponding oligomerization of fully oxygenated chains (4 β1X [unk] β4X4; ΔG0 = -22.45 ± 0.35 kcal). Hence the tetramers must bind oxygen with a higher affinity than that of dissociated chains. Calculations are presented showing why this affinity difference is not easily detected. The linkage is in a direction opposite to that exhibited by normal hemoglobin A, in which oligomerization of high-affinity unliganded dimers (2 αβ [unk] α2β2) leads to tetramers with decreased oxygen affinity. In contrast, the oligomerization of high-affinity, unliganded βSH chains leads to tetramers with even higher affinity. The results imply the existence of at least two conformational states for β chains.

Effects of inositol hexaphosphate on β chain association were investigated. Inositol hexaphosphate was found to have no measurable effect at pH 7.4, in contrast to pH 7 where very pronounced effects have been observed. Some theoretical aspects of the linkages are presented and the relationship of the findings to concepts of structural transition and allosteric regulation is discussed.

In contrast to the β chains, self-association of α chains into dimers was found to occur with the same free energy in both unliganded and fully oxygenated states. Thus, the self-association of α chains is not linked to oxygenation.

Keywords: protein association, ligand binding, thermodynamics, equilibrium gel permeation

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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