Ragtag proteins come into focus

Proteins are famous for having intricate structures that elicit specific functions, but 30-40% of protein molecules in mammalian cells are disordered enough that scientists refer to them as intrinsically unstructured proteins (IUPs). To biophysicist Richard W. Kriwacki of St. Jude Children's Research Hospital, Memphis, and his colleagues, IUPs are still as worthy of study for their cellular signaling and regulation as their rigidly structured brethren (J. Proteome Res. 2006, 5, 2839). For example, many IUPs, such as p27 (yellow), glom onto other proteins or complexes, as shown, to create functional units, Kriwacki notes. The researchers discovered that when protein extracts of mammalian cells are boiled, the more rigidly ordered proteins unfold, exposing hydrophobic interiors. As a result, the proteins clump into precipitates. Thin on hydrophobic residues, the IUPs tend to remain dissolved. The team then used gel electrophoresis to separate the IUPs, mass spectrometry and spectral matching tools to identify nearly 200 of them, and bioinformatics to assess each protein's degree of disorder. The researchers believe they have achieved "the first large-scale experimental investigation of the intrinsically unstructured mammalian proteome."