The globins: classic structures and new insights

Abstract

The oxygen-binding proteins myoglobin and haemoglobin have a special place in the history of structural biology, and, by implication, of molecular biology and molecular medicine. When the first structures of these proteins were published, in 19581 and 19602, they were the only protein structures known. And even these structures bore very little resemblance to what we now think of as ‘protein structures’. The structures were far too crude – low resolution, as structural biologists say – to reveal the positions of any of the atoms. The beautiful and meticulous hand-drawn diagrams of the myoglobin monomer and the haemoglobin tetramer in these proteins show fat sausage-like shapes representing the eight -helices of the now well-known globin fold, with the haem group nestling in between. It took the genius of the principal scientists involved in that work, Max Perutz and John Kendrew, to imagine the potential of these rather unpromising looking structures. Perutz and Kendrew were jointly awarded the Nobel Prize for Chemistry in 1962, which was a particularly good year for structural biology; Watson, Crick and Wilkins were awarded the Physiology or Medicine Nobel for the DNA structure then too.