Veronique Greenwood, Quanta Magazine
Above a certain temperature, a cell will collapse and die. One of the most straightforward explanations for this lack of heat hardiness is that the proteins essential to life — the ones that extract energy from food or sunlight, fend off invaders, destroy waste products and so on — often have beautifully precise shapes. They start as long strands, then fold into helixes, hairpins and other configurations, as dictated by the sequence of their components. These shapes play a huge role in what they do. Yet when things start to heat up, the bonds that keep protein structures together break: first the weaker ones, and then, as the temperature mounts, the stronger ones. It makes sense that a pervasive loss of protein structure would be lethal, but until recently, the details of how, or if, this kills overheated cells were unknown.
Now, however, in a true tour de force, biophysicists at ETH Zurich in Switzerland have examined the behavior of every protein in cells from four different organisms as heat increases. This study and its rich deposit of data, published recently in Science, reveal that at the temperature at which a cell dies — whether it’s a human cell or one from Escherichia coli — only a handful of key proteins fall apart. Moreover, a protein’s abundance in a cell seems to show an intriguing relationship to the protein’s stability. The studies offer a glimpse into the fundamental rules that govern the order and disorder of proteins — rules that, researchers are realizing, have implications far beyond the question of why heat kills.
Paola Picotti, the biophysicist who led the study, explained that the experiments sprang from an old, thorny question: Why do some cells survive at high temperatures while others die? The bacterium Thermus thermophilus lives happily in hot springs and even in household hot water heaters, while E. coli withers above 40 degrees Celsius (104 degrees Fahrenheit). Strong evidence implies that differences in the stability of each organism’s proteins are involved. But looking at a protein’s behavior while it is still sitting in its living cell — the ideal way to understand it — is not easy. And isolating a protein in a test tube gives only partial answers, because within the organism, proteins nestle together, altering each other’s chemistry or holding each other in the right shape. To understand what is falling apart and why, you need to look at the proteins while they are still influencing each other.