- Person
- Max Perutz
- Lived
- 1914–2002
- Field
- Molecular biology
- From
- Austrian-British
The story
Knowing the structure of haemoglobin was only the beginning for Max Perutz. He wanted to understand how it worked. Haemoglobin has evolved to take up oxygen eagerly in the lungs and release it easily in the tissues, and binding one oxygen molecule makes it easier to bind the next. Its uptake can also be changed by acidity and carbon dioxide. Because the four iron-containing haem groups that hold oxygen sit far apart in the molecule, they must somehow communicate. Perutz set out to find out how.
Through the 1960s his team at the Laboratory of Molecular Biology in Cambridge solved the atomic structures of both the oxygen-carrying and the oxygen-free forms of haemoglobin. Comparing them, Perutz in 1970 proposed a stereochemical mechanism. The molecule behaves like a machine that switches between two shapes, and the binding of oxygen triggers the change from one to the other, controlling the uptake of oxygen and its release to the muscles and other organs.
The mechanism depends on two linked movements. When oxygen attaches to the iron in a haem group, the iron atom shifts very slightly. That shift was controversial for many years because it is so small, but Perutz eventually proved it through very careful measurements. The second movement is a shift of the protein subunits relative to each other. Haemoglobin is built from two matching halves, each made of one alpha and one beta chain, and this movement is the reason crystals of oxygen-free haemoglobin break apart when they take up oxygen.
It took Perutz about 25 years to establish this basic mechanism, sifting masses of observations, some of them wrong or misleading. He told the story of these haemoglobin battles in his 1997 book Science Is Not a Quiet Life. Further work over the next two decades refined and corroborated the mechanism. In 1998, as first author of a review of how haemoglobin's oxygen binding is coordinated, he concluded that his mechanism still appeared to be correct.
Haemoglobin became the classic example of an allosteric protein, one that reversibly switches between active and inactive forms when a molecule binds to it. Perutz explored the wider principle in his 1990 book on cooperativity and allosteric regulation in proteins, and the idea of proteins as molecular switches now runs through biology and medicine.
Why it matters
Perutz's account of haemoglobin became the classic example of how proteins act as switches, a principle central to biology and drug design.
About Max Perutz
Viennese refugee who spent 22 years solving the structure of haemoglobin, won the 1962 Nobel Prize and built the Cambridge laboratory where molecular biology came of age.
More about Max Perutz
- Max Perutz founded the unit where DNA's shape was foundIn 1947 Max Perutz obtained Medical Research Council support for a small unit to study biological molecules; Watson and Crick built their DNA model there in 1953.
- Max Perutz was also a pioneering glacier scientistIn 1938 Max Perutz joined a three-man expedition to study how snow becomes glacier ice in Switzerland, work that made him an expert on glaciers.
- Perutz linked haemoglobin's shape to inherited diseaseMax Perutz studied how changes in haemoglobin's amino acids alter its function, hoping to find drugs for genetic blood disorders such as sickle cell anaemia.
- Max Perutz found the key to seeing protein structuresIn 1953 Max Perutz showed that attaching heavy atoms such as mercury to protein crystals solves the X-ray 'phase problem', making protein crystallography possible.
- In his eighties, Perutz took on Huntington's diseaseIn his final years Max Perutz studied Huntington's disease, showing that its age of onset is linked to the number of glutamine repeats, which form a 'polar zipper'.
- Perutz led a lab whose scientists shared 12 Nobel PrizesMax Perutz founded and chaired the MRC Laboratory of Molecular Biology in Cambridge from 1962 to 1979; its scientists have shared 12 Nobel Prizes.
- Max Perutz revealed the structure of haemoglobinIn 1959, 22 years after he began, Max Perutz determined the structure of haemoglobin, the blood's oxygen carrier, sharing the 1962 Nobel Prize in Chemistry.
Sources
- Max Perutz Wikipedia
- Max Perutz American Crystallographic Association history
- Max Ferdinand Perutz Physics Today
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