Hemoglobin and Cooperativity

Hemoglobin has long been a star among proteins. Along with its close cousin myoglobin, it was the first protein to have its three-dimensional structure determined -- a prodigious accomplishment by Max Perutz and his colleagues at Cambridge University in the late 1950s. Since then hemoglobin has served as a model for understanding the relationship between a protein's structure and function.

Normal adult hemoglobin is composed of four subunits linked together, with each subunit containing a single heme -- the ring-like structure with a central iron atom that binds to an oxygen atom.

In this ribbon model of hemoglobin, each of the four subunits is shown in a different color; the four heme groups are red.

The hemes -- from the Greek word for blood, haima -- are what give blood its characteristic red color. Hemoglobin structure is known for both its deoxygenated state, when it has no oxygen, and its oxygenated form -- carrying a full load of four oxygen atoms. Ho's work looks at what happens in between these two states.

Deoxy-hemoglobin is relatively uninterested in oxygen, but when one oxygen attaches, the second binds more easily, and the third and fourth easier yet. The same process works in reverse: once fully loaded hemoglobin lets go of one oxygen, it lets go of the next more easily, and so forth. This relationship -- called cooperativity -- indicates that one hemoglobin subunit transmits information to the others, and similar signaling, says Ho, occurs in other proteins. "We'd like to know the molecular basis of the oxygenation process, not only as a way to understand how hemoglobin functions, but also as a model to find out how other important proteins and enzymes regulate metabolic processes."

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