Allosteric transitions in hemoglobin revisited.

BACKGROUND

Human hemoglobin is an allosteric protein that exerts exquisite control over ligand binding through large-scale conformational changes. The two-state model without intermediates offers a simple qualitative description of the allosteric behavior of hemoglobin, as presented in textbooks. However, there is renewed interest in this topic due to recent experimental breakthroughs that show how hemoglobin actually undergoes conformational transitions in response to environmental changes.

SCOPE OF REVIEW

I review the current understanding of hemoglobin structure-function relationships revealed by recent discoveries. A unique single crystal, in which three protein molecules are allowed to express a whole range of quaternary structures, helped to reveal the detailed transition pathway including various intermediate forms. I also discuss the potential of single-molecule techniques that are currently under examination.

MAJOR CONCLUSIONS

New crystallographic approaches reveal that the hemoglobin allosteric transition involves population shifts in multiple quaternary conformers rather than a simple two-state switch, and that coexisting individual conformers may have disproportionate effects on the apparent O affinity of hemoglobin.

GENERAL SIGNIFICANCE

These approaches provide a further level of complexity on the textbook statement of hemoglobin allostery, highlighting the relevance of conformational distributions in controlling the function and regulation of allosteric proteins.