Haemoglobin: Cooperativity in Protein–Ligand Interactions
Published Online: 19 APR 2010
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Ho, C. and Yuan, Y. 2010. Haemoglobin: Cooperativity in Protein–Ligand Interactions. eLS. .
- Published Online: 19 APR 2010
Haemoglobin (Hb) is an essential component of the circulatory system of vertebrates. Its chief physiological function is to transport oxygen from the lungs to the tissues. Hb binds oxygen cooperatively, that is the affinity of the protein for the first oxygen molecule is less than that for subsequent oxygen molecules. Human adult Hb was among the first proteins whose complete three-dimensional structure was determined by X-ray crystallography and it has been used as a model for understanding allosteric proteins. Recent X-ray crystallographic and multinuclear NMR (nuclear magnetic resonance) studies of both ligated and unligated forms of Hb have shown that many structures exist in crystalline and solution states. These results have challenged the classical two-structure allosteric model of this protein. To understand Hb at the atomic level, we need to correlate the structural, dynamic and functional properties of hemoglobin in solution.
There are many T- and R-types of crystal structures of unligated and ligated forms of haemoglobin, in contrast to the classical two-structure model for haemoglobin allostery.
The structures of haemoglobin in both unligated and ligated forms in solution are different from those in crystals and exist as dynamic ensembles of various structures.
The ligand-binding data for proximal histidyl-detached recombinant haemoglobins show that Perutz's proximal histidyl coupling mechanism contributes approximately two-thirds to the total interaction energy between haems and that there are alternative coupling pathways for the remaining third.
The Bohr effect, a heterotropic effect, is an excellent example of a global network of electrostatic interactions, rather than a few specific amino acid residues, that play a dominant role in an important physiological function of haemoglobin.
Recent experimental results strongly suggest that allosteric proteins, such as haemoglobin, may require multiple pathways for signal communication, as is illustrated in the cooperative oxygenation and in the Bohr effect.
Haemoglobin is a molecule with considerable plasticity.
The classical two-structure mechanism for haemoglobin allostery cannot account for the structure, dynamics and function of the haemoglobin molecule and needs revision.
- allosteric interactions;
- Bohr effect;
- haemoglobin structure–dynamics–function relationship;
- crystal structures of haemoglobin determined by X-ray crystallography;
- solution structures of haemoglobin determined by multinuclear NMR spectroscopy