Self-association of hemoglobin betaSH chains is linked to oxygenation.
Self-association of unliganded beta(SH) chains into tetramers (4 beta(1) [unk] beta(4)) is experimentally found to be energetically less favorable (DeltaG(0) = -19.05 +/- 0.30 kcal) than the corresponding oligomerization of fully oxygenated chains (4 beta(1)X [unk] beta(4)X(4); DeltaG(0) = -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 alphabeta [unk] alpha(2)beta(2)) leads to tetramers with decreased oxygen affinity. In contrast, the oligomerization of high-affinity, unliganded beta(SH) chains leads to tetramers with even higher affinity. The results imply the existence of at least two conformational states for beta chains. Effects of inositol hexaphosphate on beta 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 beta chains, self-association of alpha chains into dimers was found to occur with the same free energy in both unliganded and fully oxygenated states. Thus, the self-association of alpha chains is not linked to oxygenation.
D006441:Hemoglobin A; D006454:Hemoglobins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D010108:Oxyhemoglobins; D010833:Phytic Acid; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
D006454:Hemoglobins; D008024:Ligands; D010108:Oxyhemoglobins; D010833:Phytic Acid; D006441:Hemoglobin A