Searchlight Falls On The Dark Proteome

Many protein structures have been experimentally determined, and others can be guessed from the similarity of the sequences to known protein structures. But a substantial number of proteins or pieces of proteins still lack any structural information. A team led by Seán I. O’Donoghue of Australia’s Commonwealth Scientific & Industrial Research Organisation computationally mapped this structurally deficient collection—the so-called dark proteome—and found that close to half of eukaryotic and viral proteomes are dark, compared with only 14% of archaeal and bacterial proteomes (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1073/pnas.1508380112). Some of the dark proteome comprises regions of proteins for which some structure is otherwise known, but nearly half of it encompasses proteins for which there is no structural information at all. And the researchers don’t know why most of those proteins are dark because conventional explanations for lack of protein structural information, such as their intrinsic disorder and transmembrane regions, account for only a small fraction of the dark proteome. The researchers determined that many dark proteins are secreted proteins that reside in the extracellular space. “Knowing where to look for them will certainly help in studying their structures and helping them become nondark,” O’Donoghue says.