The proteins that unravel as the temperature starts to rise turn out to be among the most vital.
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.