Editing Hemoglobin (section)

==Cooperativity==
[[File:Hemoglobin t-r state ani.gif|frame|A schematic visual model of oxygen-binding process, showing all four [[monomer]]s and [[heme]]s, and [[protein|protein chains]] only as diagrammatic coils, to facilitate visualization into the molecule. [[Oxygen]] is not shown in this model, but, for each of the [[iron]] atoms, it binds to the iron (red sphere) in the flat [[heme]]. For example, in the upper-left of the four hemes shown, oxygen binds at the left of the iron atom shown in the upper-left of diagram. This causes the iron atom to move backward into the heme that holds it (the iron moves upward as it binds oxygen, in this illustration), tugging the [[histidine]] residue (modeled as a red pentagon on the right of the iron) closer, as it does. This, in turn, pulls on the protein chain holding the [[histidine]].]]

When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the [[porphyrin]] ring (see moving diagram). At the same time, the [[imidazole]] side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in the protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier.

As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes the binding of oxygen to the remaining three monomers' heme groups, thus saturating the hemoglobin molecule with oxygen.<ref>{{cite journal |last1=Mihailescu |first1=Mihaela-Rita |last2=Russu |first2=Irina M. |date=2001-03-27 |title=A signature of the T → R transition in human hemoglobin |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=98 |issue=7 |pages=3773–77 |issn=0027-8424 |bibcode=2001PNAS...98.3773M |pmid=11259676 |doi=10.1073/pnas.071493598 |doi-access=free |pmc=31128}}</ref>

In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a [[cooperative binding|cooperative process]]. The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for the next ones, in a way favorable for binding. This positive cooperative binding is achieved through [[steric effects|steric]] conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin is [[sigmoid function|sigmoidal]], or ''S''-shaped, as opposed to the normal [[hyperbolic function|hyperbolic]] curve associated with noncooperative binding.

The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency [[resonance]] has been discussed.<ref name="Chou-1989">{{cite journal |author=Chou KC |title=Low-frequency resonance and cooperativity of hemoglobin |journal=Trends Biochem. Sci. |volume=14 |issue=6 |pages=212–13 |year=1989 |pmid=2763333 |doi=10.1016/0968-0004(89)90026-1}}</ref>