Single residue modification of only one dimer within the hemoglobin tetramer reveals autonomous dimer function.

The mechanism of cooperativity in the human hemoglobin tetramer (a dimer of alpha beta dimers) has historically been modeled as a simple two-state system in which a low-affinity structural form (T) switches, on ligation, to a high-affinity form (R), yielding a net loss of hydrogen bonds and salt bridges in the dimer-dimer interface. Modifications that weaken these cross-dimer contacts destabilize the quaternary T tetramer, leading to decreased cooperativity and enhanced ligand affinity, as demonstrated in many studies on symmetric double modifications, i.e.