How a sperm whale muscle helped reveal the secret architecture of life
In short: In the 1950s, scientists set out to map the first protein structures. While the goal was ambitious, the breakthrough required looking beyond the laboratory to the deep ocean, using the massive oxygen reserves of whales to solve a biological mystery.
During the 1950s, a period defined by the Cold War and the rise of rock and roll, structural biology underwent a revolution. In Cambridge, John Kendrew and his team sought to establish the first molecular structure of a protein. They chose myoglobin—a molecule a quarter the size of haemoglobin—because its smaller scale offered a more manageable starting point for their experiments.
The primary challenge was not just finding the protein, but obtaining crystals large enough for X-ray analysis. Initial attempts using horse heart myoglobin failed because the crystals were too small. Kendrew realized that diving animals, which require higher oxygen storage in their muscles, might provide a better source. After testing samples from creatures like penguins, he found that a chunk of sperm whale muscle yielded large crystals with clean X-ray diffraction patterns.
The process of interpreting the resulting data was equally arduous. To overcome the 'phase problem,' Kendrew attached heavy metals to five distinct sites on the molecule. At a resolution of 6 Å, the team could see the overall layout and the haem group as a simple disk of electron density. However, as they increased the resolution to 2 Å, the complexity grew exponentially. Kendrew had to pioneer the use of early computers to manage tens of thousands of data points.
This higher resolution revealed the protein's secondary structure, specifically the presence of right-handed α-helices, and allowed the team to resolve the iron atom from the nitrogens of the porphyrin ring. This precision corrected previous misinterpretations of the haem group's orientation and confirmed that the iron atom bonds to a nitrogen atom in a histidine residue. This work transformed our understanding of how proteins like myoglobin, encoded on chromosome 2 .2, function to store oxygen in our muscles.
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Sources
- Summary by Intellect · source: Chromosome 22 - Myoglobin (a brief history of structural biology)
- Also: It all started with myoglobin | Protein Data Bank in Europe
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