How to Kill a Protein

For decades scientists have been looking closely at how our cells make proteins. But the inverse is equally important: how cells kill them.

While producing healthy, vital proteins is fundamental to life, cells also destroy proteins as a way to switch essential processes on and off. What’s more, cells often need to dispose of proteins that malfunction. In fact, protein destruction has emerged as one of the most significant regulatory mechanisms in cells, equal to protein production. There are also many conditions and diseases, such as neurodegeneration, that result when our bodies can’t efficiently take out the proteomic trash or destroy a protein in order to flip a critical switch. 



We certainly know much more about how proteins are made than we do about how they are unmade, but knowledge of the latter is catching up. Researchers in the lab of Marc Kirschner, chair of the Department of Systems Biology at Harvard Medical School, have recently published twin papers that describe, at the resolution of single molecules, the dynamic process of protein degradation.

The researchers comment that this process bears many similarities to speed dating.

The studies are published in the journal Science.

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There are many players involved in the act of destroying a protein. A molecular complex called anaphase-promoting complex, or APC, choreographs the intricate events in cell division by sequentially destroying key proteins that block progression of this process. At the right time, APC tags its target with a small protein called ubiquitin. This tagging, a kiss of death, signals a cellular machine called the proteasome.

The proteasome is like a blender stuck on one setting: puree. It is a blunt, and brute, instrument that pulverizes whatever gets inside. Once it smells a ubiquitin tag of a certain type, the protein doesn’t stand a chance.

Well, sort of.

Knowledge to date of this process is based on protocols that amass interactions from millions of cells and create static data points that describe a simple, linear process. APC tags a protein with ubiquitin, proteasome shreds the protein. But such data are really no more than a snapshot.

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